胆碱酯酶抑制剂类农药的神经毒性及机制研究
|
摘要
本课题作为国家科技支撑项目《农药及内分泌干扰物的复合效应评估技术研究》(2006BAK02A02)的子课题,重点研究了有机磷农药毒死蜱(chlorpyrifos,CPF)染毒一段时间后撤除对海马神经元的毒性作用与作用机制,以及海马神经元对CPF的耐受作用,为有机磷农药的慢性神经毒性作用机制研究提供理论依据;并研究了氨基甲酸酯农药克百威(carbofuran,CBF)预处理对CPF细胞毒性的影响及作用机制,以及氧化应激在该过程中的作用,为氨基甲酸酯农药与有机磷农药联合作用提供依据。
1.毒死蜱撤除引起的海马神经元毒性与ERK1/2磷酸化抑制及乙酰胆碱神经系统功能不足有关
有机磷农药诱导的慢性神经毒性(organophosphate induced chronicneurotoxicity,OPICN)具有迟发性,并持续很长时间,机制不明。为探讨这种慢性神经毒性的作用机制,本文研究了CPF撤除对原代培养海马神经元的毒性作用及相关机制。结果显示,10μM CPF连续染毒达96 h未产生明显细胞毒性,但在染毒48 h后将CPF撤除,却可导致明显的细胞毒性,表现为撤除CPF后24或48 h(自染毒计时为72 h或96 h),神经元MTT代谢降低,神经元缺失增加,TUNEL阳性细胞增加。10μM CPF染毒对神经元胆碱酯酶(AChE)活性产生抑制作用,在CPF撤除后,AChE活性轻度升高,提示由CPF撤除引起的细胞毒性不是AChE抑制的直接结果。CPF染毒可使ERK1/2经磷酸化激活,在CPF存在的情况下,这种激活作用可持续数小时,以后逐渐恢复正常,染毒48 h后CPF撤除使ERK1/2磷酸化受到抑制。氨甲酰胆碱与神经生长因子(NGF)可激活ERK1/2,对CPF撤除后的细胞具有保护作用;阿托品与PD98059抑制ERK1/2磷酸化,加重了CPF撤除后的细胞毒性,显示抑制ERK1/2磷酸化在CPF撤除导致的细胞毒性中起重要作用。氨甲酰胆碱是一种胆碱能激动剂,阿托品是胆碱能拮抗剂,两者对CPF撤除后细胞毒性以及AChE的变化都提示CPF撤除引起了乙酰胆碱神经系统功能不足。结论:10μM CPF连续染毒96h无细胞毒性,但染毒48 h后撤除导致明显的细胞毒性,这种细胞毒性不是AChE抑制所致,而与ERK1/2磷酸化抑制及乙酰胆碱神经系统功能不足有关。提示CPF撤除可能引起戒断反应,有机磷农药的慢性神经毒性可能与戒断作用有关。
2.海马神经元对毒死蜱的耐受作用研究
在研究1中发现,无细胞毒性浓度的CPF染毒一段时间后撤除可以导致细胞毒性,提示有机磷农药可能会产生戒断毒性。由于耐受作用往往是戒断作用的前提,为进一步探讨有机磷农药的毒性作用机制,有必要对有机磷农药的耐受作用进行深入研究。我们采用无细胞毒性浓度(10μM)CPF对培养海马神经元预处理染毒48 h,再经较高浓度的CPF(30,60,100 gM)染毒48 h,通过测定细胞存活率、LDH漏出率以及Tunel阳性细胞率,比较是否CPF预处理一段时间可以降低较高浓度CPF对细胞的毒性作用。结果:经10μM CPF预处理组比未经预处理组细胞存活率上升、LDH漏出率下降、Tunel阳性细胞率下降,表明经预处理的细胞对较高浓度的CPF产生了耐受作用。本研究进一步提示CPF撤除引起的细胞毒性作用是一种戒断反应,提示有机磷农药导致的慢性神经毒性可能与戒断反应有关。
3.氨基甲酸酯农药克百威预处理对有机磷农药毒死蜱神经细胞毒性的影响
农业生产中大量使用有机磷农药与氨基甲酸酯农药,使得人类暴露于这两类农药的机会增加,尤其是可在不同时间暴露于这两类农药,从而产生联合作用。为探讨这两类农药的联合作用与机制,我们研究氨基甲酸酯农药CBF预处理对有机磷农药CPF神经细胞毒性的影响。方法:采用MTT法测定CBF处理后原代培养皮层神经细胞存活率,找出无细胞毒性浓度;采用无毒浓度的CBF对培养细胞进行不同时间的预处理,再加入CPF染毒48 h(同时存在CBF)测定细胞毒性变化;采用Western blot方法研究CBF不同时间预处理对CPF激活ERK1/2作用的影响。结果:10μM CBF染毒72 h显示无细胞毒性,10μM CBF预处理2～24 h可减轻60μM CPF的毒性,预处理8 h作用最强;CBF预处理降低了CPF对ERK1/2的激活作用,抑制ERK1/2激活作用与细胞毒性减轻相关。而CBF与CPF同时染毒(预处理0h)对CPF的细胞毒性及ERK1/2激活影响很小。结论:CBF预处理一段时间后可拮抗CPF的细胞毒性,作用机制与抑制ERK1/2激活有关,而CBF预处理时间过短,则不产生拮抗作用。提示氨基甲酸酯农药与有机磷农药之间的联合作用模式受两者暴露时间间隔影响。
4.克百威预处理对毒死蜱致皮层神经细胞氧化应激作用的影响在前面的研究中,10μM CBF对皮层神经细胞预处理8 h可显著减轻CPF的细胞毒性,由于氧化应激作用与农药的毒性有关,本研究进一步探讨了氧化应激在该过程中的作用,以揭示有机磷农药与氨基甲酸酯农药联合作用的机制。方法:以10μM CBF染毒原代培养皮层神经细胞8 h,测定丙二醛(MDA)水平、谷胱甘肽(GSH)水平、超氧化物岐化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-PX)活性;以10μM CBF对皮层神经细胞染毒8 h后,再以不同浓度CPF(20、40、60、80μM)染毒24 h,测定上述氧化应激指标。结果:CBF染毒8 h,可使MDA水平轻度增加,SOD、GSH-PX活性升高,GSH水平无显著变化;在无CBF预处理情况下,CPF染毒可使皮层神经细胞MDA水平增加,GSH水平下降,SOD、GSH-PX活性下降,呈现明显的浓度-效应关系,表明CPF可使神经细胞产生明显的氧化应激作用。CBF预处理对CPF所致氧化应激作用产生影响,与未经CPF预处理组比较,CBF预处理组MDA下降,GSH水平有所升高,SOD、GSH-PX活性升高,表明经CBF预处理的细胞对CPF的氧化损伤具有抵抗作用。结论:CBF预处理可拮抗CPF的脂质过氧化损伤作用,作用机制可能与CBF诱导产生轻度的氧化应激作用,在产生轻度过氧化损伤导致MDA升高的同时,增强了细胞的抗氧化能力有关,提示氧化应激作用参与了农药之间的联合作用机制。
结论:
1.CPF可诱导海马神经元的耐受作用,以无毒性作用浓度的CPF染毒一段时间后撤除可产生细胞毒性,这种CPF撤除所致细胞毒性作用与ERK1/2磷酸化抑制及乙酰胆碱神经系统功能不足有关,提示有机磷的慢性神经毒性可能与戒断作用有关。
2.以无细胞毒性作用浓度的CBF预处理一段时间后可以拮抗CPF对皮层神经细胞的毒性作用,作用机制与CBF预处理可以抑制CPF的ERK1/2激活作用及减轻了CPF所致氧化应激作用有关。提示氨基甲酸酯农药与有机磷农药之间的联合作用模式受两者暴露时间间隔影响。
This project is a part of the China National Scientific Supporting Program (Technical Research for Evaluating Combined Action of Pesticides or Endocrine Discrupting Substances)(2006BAK02A02).It firstly focused on study of chlorpyrifos (CPF) withdrawal-induced cytotoxicity after a period of exposure in hippocampal neurons,and tolerance of neurons to CPF,which will help to explain the mechanism of organophosphate induced chronic neurotoxicity(OPICN);It secondly focused on study of the effects of carbamate carbofuran pretreatment on organophosphorus CPF-induced cytotoxicity,and role of oxidative stress in this process,which will provide information about combined action of organophosphorus pesticide and carbamate pesticide.
1.Chlorpyrifos withdrawal induces cytotoxicity in primary hippocampal neurons related to inhibition of ERK1/2 phosphorylation and cholinergic deficit
Organophosphate-induced chronic neurotoxicity(OPICN) usually delayed-occurs and perisists long,its mechanism is not very clear.In present study,the cytotoxicity and related mechanisms after CPF withdrawal were studied in primary rat hippocampal neurons.The results showed that 10μM CPF induced no detectable cytotoxicity during 96 h continuous exposure,but 10μM CPF withdrawal after 48 h exposure induced evident cytotoxicity,as indexed by decreased MTT metabolism, increased loss of neurons immunostained by neuron-specific enolase(NSE) antibody, and increased TUNEL positive cell rate in the following 24 h and 48 h incubation in the absence of CPF.AChE activity was inhibited by 10μM CPF during exposure,it slightly recovered after CPF withdrawal,suggesting CPF withdrawal-induced cytotoxicity is not direct consequence of inhibited AChE.ERK1/2 activation by phosphorylation was found,it persisted hours and then resumed to normal level during CPF exposure,while CPF withdrawal after 48 h exposure led to inhibition of ERK1/2 phosphorylation.Carbacol and NGF which activated ERK1/2 protected the neurons after CPF withdrawal,while atropine and PD98059 which inhibited ERK1/2 exacerbated the cytotoxicity after CPF withdrawal,indicating inhibition of ERK1/2 phosphorylation played critical role in CPF induced withdrawal-induced cytotoxicity. The effects of carbacol which is a cholinergic agonist,and atropine which is a cholinergic antagonist,also suggest cholinergic deficit involve in the mechanism of CPF withdrawal-induced cytotoxicity.In conclusion,10μM CPF shows noncytotoxic during 96 h exposure,but CPF withdrawal after 48 h exposure induces cytotoxicity in cultured neurons,which is not related to AChE inhibition,but is associated with ERK1/2 inhibition and cholinergic deficit.The results suggest CPF withdrawal-induced cytotoxicity is a kind of withdrawal effect,and OPICN may be related to withdrawal syndrome.
2.Tolerance study of hippocampal neurons to CPF
In Part 1 study,the results showed non-cytotoxic CPF withdrawal after a period of exposure induced cytotoxicity,and suggested CPF induce withdrawal effect.Since tolerance is prerequisite of withdrawal effect,we studied whether CPF could induce tolerance in cultured hippocampal neurons to further elucidate the mechanism of CPF withdrawal-induced cytotoxicity.Method:the cultured hippocampal neurons were pretreated with 10μM CPF for 48 h,then,the neurons were exposed to high concentration of CPF(30,60,100μM CPF) for the following 48 h incubation,and cytotoxicity was measured.Result:the survival rate measured by MTT assay increased,the LDH leakage decreased,and Tunel positive rate decreased in noncytotoxic CPF pretreatment groups,compared with corresponding groups without CPF pretreatment.Conclusion:CPF pretreatment induces tolerance of neurons, confirming the cytotoxitiy after CPF withdrawal is related to withdrawal effect,and suggesting OPICN be related to withdrawal syndrome.
3.Effects of carbamate carbofuran pretreatment on organophosphate chlorpyrifos-induced cytotoxicity in cortical neural cells
Organophosphorus pesticides and cabarmate pesticides are used extensively in agriculture,resulting in pervasive human exposure,sequential or simultaneous exposure to the two kinds of pesticides leads combined action.To investigate the combined action of organophosphorus pesticide and cabarmate pesticide,in this study, the effect of carbofuran pretreatment on CPF-induced cytotoxicity and related mechanism were studied.Methods:primarily cultured cortical neural cells were exposed to various doses of carbofuran for 72 h,cytotoxicity was measured by MTT method,and a noncytotoxic level was determined.The cultured cells were pretreated with noncytotoxic level of carbofuran for different period,followed by exposure to various concentration of CPF(with CBF presence) for 48 h,and the cytotoxicity were measured.The effect of carbofuran pretreatment on CPF-induced ERK1/2 activation was examed by western blot assay.Results:10μM carbofuran was found nontoxic during 72 h exposure.10μM carbofuran pretreatment attenuated CPF-induced cytotoxicity,8 h carbofuran pretreatment showed the maximum effect;Carbofuran activated ERK1/2,and the ERK1/2 activation lasted shortly,while carbofuran 2-24 h pretreatment inhibited the CPF-induced ERK1/2 activation,which was corresponding to the cytotoxicity attenuation.While concomitant exposure of carbofuran (pretreatment time 0 h) and CPF induced no significant effect on CPF induced cytotoxicity and ERK1/2 activation.Conclusion:Carbofuran pretreatment for certain time antagonize CPF-induced cytotoxicity,which is related to the inhibition of ERK1/2 activation,but carbofuran does not antagonize the cytotoxicity induced by CPF when the two pesticides exposed simultaneously,suggesting the mode of combined action is affected by the exposure interval between the two pesticides.
4.Effects of carbamate carbofuran pretreatment on organophosphorus chlorpyrifos-induced oxidative stress in cortical neural cells
In part 3 study,10μM carbofuran pretreatment for 8 h antagonized the cytotoxicity induced by CPF,since oxidative stress is involved extensively in the toxicity of pesticides,we study the role of oxidative stress in the process of carbofuran pretreatment antagonizing CPF toxicity.Method:the neural cells were pretreated with 10μM carbofuran for 8 h,the oxidative stress indices MDA,SOD, GSH and GSH-PX were measured.After 8 h carbofuran pretreatment,the cells were treated with different concentration(20、40、60、80μM) of CPF for another 24 h,and the same indices as previous were measured.Result:Carbofuran treatment for 8 h inceased MDA level sightly but significantly,increased SOD and GSH-PX activity, and induced no obvious change in GSH level;CPF exposure inceased MDA level, and decreased SOD activity,GSH-PX activity and GSH level with a concentration—response mannner;CPF with carbofuran pretreatment decreased MDA level,and increased SOD activity,GSH-PX activity and GSH level,compared to that without carbofuran pretreatment.Conclusion:carbofuran pretreatment antagonizes CPF induced lipid peroxidative damage,the mechanism may be related to that carbofuran induces slightly oxidative stress and increases the anti-oxidative enzymes activity.
Conclusion:
1.Noncytotoxic concentration of CPF can induce tolerance of hippocampal neurons,and induces cytotoxicity after withdrawal,while ERK inhibition and cholinergic deficit are related to the mechanism of CPF withdrawal induced cytotoxicity,suggesting OPICN be related to withdrawal symptom.
2.Carbofuran pretreatment can antagonize cytotoxicity induced by chlopyrifos in neronal cells,with the mechansim involving that carbofuran pretreatment reduces ERK1/2 activation and oxidative stress induced by CPF,suggesting the mode of combined action is affected by the exposure interval between the two pesticides.
1.毒死蜱撤除引起的海马神经元毒性与ERK1/2磷酸化抑制及乙酰胆碱神经系统功能不足有关
有机磷农药诱导的慢性神经毒性(organophosphate induced chronicneurotoxicity,OPICN)具有迟发性,并持续很长时间,机制不明。为探讨这种慢性神经毒性的作用机制,本文研究了CPF撤除对原代培养海马神经元的毒性作用及相关机制。结果显示,10μM CPF连续染毒达96 h未产生明显细胞毒性,但在染毒48 h后将CPF撤除,却可导致明显的细胞毒性,表现为撤除CPF后24或48 h(自染毒计时为72 h或96 h),神经元MTT代谢降低,神经元缺失增加,TUNEL阳性细胞增加。10μM CPF染毒对神经元胆碱酯酶(AChE)活性产生抑制作用,在CPF撤除后,AChE活性轻度升高,提示由CPF撤除引起的细胞毒性不是AChE抑制的直接结果。CPF染毒可使ERK1/2经磷酸化激活,在CPF存在的情况下,这种激活作用可持续数小时,以后逐渐恢复正常,染毒48 h后CPF撤除使ERK1/2磷酸化受到抑制。氨甲酰胆碱与神经生长因子(NGF)可激活ERK1/2,对CPF撤除后的细胞具有保护作用;阿托品与PD98059抑制ERK1/2磷酸化,加重了CPF撤除后的细胞毒性,显示抑制ERK1/2磷酸化在CPF撤除导致的细胞毒性中起重要作用。氨甲酰胆碱是一种胆碱能激动剂,阿托品是胆碱能拮抗剂,两者对CPF撤除后细胞毒性以及AChE的变化都提示CPF撤除引起了乙酰胆碱神经系统功能不足。结论:10μM CPF连续染毒96h无细胞毒性,但染毒48 h后撤除导致明显的细胞毒性,这种细胞毒性不是AChE抑制所致,而与ERK1/2磷酸化抑制及乙酰胆碱神经系统功能不足有关。提示CPF撤除可能引起戒断反应,有机磷农药的慢性神经毒性可能与戒断作用有关。
2.海马神经元对毒死蜱的耐受作用研究
在研究1中发现,无细胞毒性浓度的CPF染毒一段时间后撤除可以导致细胞毒性,提示有机磷农药可能会产生戒断毒性。由于耐受作用往往是戒断作用的前提,为进一步探讨有机磷农药的毒性作用机制,有必要对有机磷农药的耐受作用进行深入研究。我们采用无细胞毒性浓度(10μM)CPF对培养海马神经元预处理染毒48 h,再经较高浓度的CPF(30,60,100 gM)染毒48 h,通过测定细胞存活率、LDH漏出率以及Tunel阳性细胞率,比较是否CPF预处理一段时间可以降低较高浓度CPF对细胞的毒性作用。结果:经10μM CPF预处理组比未经预处理组细胞存活率上升、LDH漏出率下降、Tunel阳性细胞率下降,表明经预处理的细胞对较高浓度的CPF产生了耐受作用。本研究进一步提示CPF撤除引起的细胞毒性作用是一种戒断反应,提示有机磷农药导致的慢性神经毒性可能与戒断反应有关。
3.氨基甲酸酯农药克百威预处理对有机磷农药毒死蜱神经细胞毒性的影响
农业生产中大量使用有机磷农药与氨基甲酸酯农药,使得人类暴露于这两类农药的机会增加,尤其是可在不同时间暴露于这两类农药,从而产生联合作用。为探讨这两类农药的联合作用与机制,我们研究氨基甲酸酯农药CBF预处理对有机磷农药CPF神经细胞毒性的影响。方法:采用MTT法测定CBF处理后原代培养皮层神经细胞存活率,找出无细胞毒性浓度;采用无毒浓度的CBF对培养细胞进行不同时间的预处理,再加入CPF染毒48 h(同时存在CBF)测定细胞毒性变化;采用Western blot方法研究CBF不同时间预处理对CPF激活ERK1/2作用的影响。结果:10μM CBF染毒72 h显示无细胞毒性,10μM CBF预处理2～24 h可减轻60μM CPF的毒性,预处理8 h作用最强;CBF预处理降低了CPF对ERK1/2的激活作用,抑制ERK1/2激活作用与细胞毒性减轻相关。而CBF与CPF同时染毒(预处理0h)对CPF的细胞毒性及ERK1/2激活影响很小。结论:CBF预处理一段时间后可拮抗CPF的细胞毒性,作用机制与抑制ERK1/2激活有关,而CBF预处理时间过短,则不产生拮抗作用。提示氨基甲酸酯农药与有机磷农药之间的联合作用模式受两者暴露时间间隔影响。
4.克百威预处理对毒死蜱致皮层神经细胞氧化应激作用的影响在前面的研究中,10μM CBF对皮层神经细胞预处理8 h可显著减轻CPF的细胞毒性,由于氧化应激作用与农药的毒性有关,本研究进一步探讨了氧化应激在该过程中的作用,以揭示有机磷农药与氨基甲酸酯农药联合作用的机制。方法:以10μM CBF染毒原代培养皮层神经细胞8 h,测定丙二醛(MDA)水平、谷胱甘肽(GSH)水平、超氧化物岐化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-PX)活性;以10μM CBF对皮层神经细胞染毒8 h后,再以不同浓度CPF(20、40、60、80μM)染毒24 h,测定上述氧化应激指标。结果:CBF染毒8 h,可使MDA水平轻度增加,SOD、GSH-PX活性升高,GSH水平无显著变化;在无CBF预处理情况下,CPF染毒可使皮层神经细胞MDA水平增加,GSH水平下降,SOD、GSH-PX活性下降,呈现明显的浓度-效应关系,表明CPF可使神经细胞产生明显的氧化应激作用。CBF预处理对CPF所致氧化应激作用产生影响,与未经CPF预处理组比较,CBF预处理组MDA下降,GSH水平有所升高,SOD、GSH-PX活性升高,表明经CBF预处理的细胞对CPF的氧化损伤具有抵抗作用。结论:CBF预处理可拮抗CPF的脂质过氧化损伤作用,作用机制可能与CBF诱导产生轻度的氧化应激作用,在产生轻度过氧化损伤导致MDA升高的同时,增强了细胞的抗氧化能力有关,提示氧化应激作用参与了农药之间的联合作用机制。
结论:
1.CPF可诱导海马神经元的耐受作用,以无毒性作用浓度的CPF染毒一段时间后撤除可产生细胞毒性,这种CPF撤除所致细胞毒性作用与ERK1/2磷酸化抑制及乙酰胆碱神经系统功能不足有关,提示有机磷的慢性神经毒性可能与戒断作用有关。
2.以无细胞毒性作用浓度的CBF预处理一段时间后可以拮抗CPF对皮层神经细胞的毒性作用,作用机制与CBF预处理可以抑制CPF的ERK1/2激活作用及减轻了CPF所致氧化应激作用有关。提示氨基甲酸酯农药与有机磷农药之间的联合作用模式受两者暴露时间间隔影响。
This project is a part of the China National Scientific Supporting Program (Technical Research for Evaluating Combined Action of Pesticides or Endocrine Discrupting Substances)(2006BAK02A02).It firstly focused on study of chlorpyrifos (CPF) withdrawal-induced cytotoxicity after a period of exposure in hippocampal neurons,and tolerance of neurons to CPF,which will help to explain the mechanism of organophosphate induced chronic neurotoxicity(OPICN);It secondly focused on study of the effects of carbamate carbofuran pretreatment on organophosphorus CPF-induced cytotoxicity,and role of oxidative stress in this process,which will provide information about combined action of organophosphorus pesticide and carbamate pesticide.
1.Chlorpyrifos withdrawal induces cytotoxicity in primary hippocampal neurons related to inhibition of ERK1/2 phosphorylation and cholinergic deficit
Organophosphate-induced chronic neurotoxicity(OPICN) usually delayed-occurs and perisists long,its mechanism is not very clear.In present study,the cytotoxicity and related mechanisms after CPF withdrawal were studied in primary rat hippocampal neurons.The results showed that 10μM CPF induced no detectable cytotoxicity during 96 h continuous exposure,but 10μM CPF withdrawal after 48 h exposure induced evident cytotoxicity,as indexed by decreased MTT metabolism, increased loss of neurons immunostained by neuron-specific enolase(NSE) antibody, and increased TUNEL positive cell rate in the following 24 h and 48 h incubation in the absence of CPF.AChE activity was inhibited by 10μM CPF during exposure,it slightly recovered after CPF withdrawal,suggesting CPF withdrawal-induced cytotoxicity is not direct consequence of inhibited AChE.ERK1/2 activation by phosphorylation was found,it persisted hours and then resumed to normal level during CPF exposure,while CPF withdrawal after 48 h exposure led to inhibition of ERK1/2 phosphorylation.Carbacol and NGF which activated ERK1/2 protected the neurons after CPF withdrawal,while atropine and PD98059 which inhibited ERK1/2 exacerbated the cytotoxicity after CPF withdrawal,indicating inhibition of ERK1/2 phosphorylation played critical role in CPF induced withdrawal-induced cytotoxicity. The effects of carbacol which is a cholinergic agonist,and atropine which is a cholinergic antagonist,also suggest cholinergic deficit involve in the mechanism of CPF withdrawal-induced cytotoxicity.In conclusion,10μM CPF shows noncytotoxic during 96 h exposure,but CPF withdrawal after 48 h exposure induces cytotoxicity in cultured neurons,which is not related to AChE inhibition,but is associated with ERK1/2 inhibition and cholinergic deficit.The results suggest CPF withdrawal-induced cytotoxicity is a kind of withdrawal effect,and OPICN may be related to withdrawal syndrome.
2.Tolerance study of hippocampal neurons to CPF
In Part 1 study,the results showed non-cytotoxic CPF withdrawal after a period of exposure induced cytotoxicity,and suggested CPF induce withdrawal effect.Since tolerance is prerequisite of withdrawal effect,we studied whether CPF could induce tolerance in cultured hippocampal neurons to further elucidate the mechanism of CPF withdrawal-induced cytotoxicity.Method:the cultured hippocampal neurons were pretreated with 10μM CPF for 48 h,then,the neurons were exposed to high concentration of CPF(30,60,100μM CPF) for the following 48 h incubation,and cytotoxicity was measured.Result:the survival rate measured by MTT assay increased,the LDH leakage decreased,and Tunel positive rate decreased in noncytotoxic CPF pretreatment groups,compared with corresponding groups without CPF pretreatment.Conclusion:CPF pretreatment induces tolerance of neurons, confirming the cytotoxitiy after CPF withdrawal is related to withdrawal effect,and suggesting OPICN be related to withdrawal syndrome.
3.Effects of carbamate carbofuran pretreatment on organophosphate chlorpyrifos-induced cytotoxicity in cortical neural cells
Organophosphorus pesticides and cabarmate pesticides are used extensively in agriculture,resulting in pervasive human exposure,sequential or simultaneous exposure to the two kinds of pesticides leads combined action.To investigate the combined action of organophosphorus pesticide and cabarmate pesticide,in this study, the effect of carbofuran pretreatment on CPF-induced cytotoxicity and related mechanism were studied.Methods:primarily cultured cortical neural cells were exposed to various doses of carbofuran for 72 h,cytotoxicity was measured by MTT method,and a noncytotoxic level was determined.The cultured cells were pretreated with noncytotoxic level of carbofuran for different period,followed by exposure to various concentration of CPF(with CBF presence) for 48 h,and the cytotoxicity were measured.The effect of carbofuran pretreatment on CPF-induced ERK1/2 activation was examed by western blot assay.Results:10μM carbofuran was found nontoxic during 72 h exposure.10μM carbofuran pretreatment attenuated CPF-induced cytotoxicity,8 h carbofuran pretreatment showed the maximum effect;Carbofuran activated ERK1/2,and the ERK1/2 activation lasted shortly,while carbofuran 2-24 h pretreatment inhibited the CPF-induced ERK1/2 activation,which was corresponding to the cytotoxicity attenuation.While concomitant exposure of carbofuran (pretreatment time 0 h) and CPF induced no significant effect on CPF induced cytotoxicity and ERK1/2 activation.Conclusion:Carbofuran pretreatment for certain time antagonize CPF-induced cytotoxicity,which is related to the inhibition of ERK1/2 activation,but carbofuran does not antagonize the cytotoxicity induced by CPF when the two pesticides exposed simultaneously,suggesting the mode of combined action is affected by the exposure interval between the two pesticides.
4.Effects of carbamate carbofuran pretreatment on organophosphorus chlorpyrifos-induced oxidative stress in cortical neural cells
In part 3 study,10μM carbofuran pretreatment for 8 h antagonized the cytotoxicity induced by CPF,since oxidative stress is involved extensively in the toxicity of pesticides,we study the role of oxidative stress in the process of carbofuran pretreatment antagonizing CPF toxicity.Method:the neural cells were pretreated with 10μM carbofuran for 8 h,the oxidative stress indices MDA,SOD, GSH and GSH-PX were measured.After 8 h carbofuran pretreatment,the cells were treated with different concentration(20、40、60、80μM) of CPF for another 24 h,and the same indices as previous were measured.Result:Carbofuran treatment for 8 h inceased MDA level sightly but significantly,increased SOD and GSH-PX activity, and induced no obvious change in GSH level;CPF exposure inceased MDA level, and decreased SOD activity,GSH-PX activity and GSH level with a concentration—response mannner;CPF with carbofuran pretreatment decreased MDA level,and increased SOD activity,GSH-PX activity and GSH level,compared to that without carbofuran pretreatment.Conclusion:carbofuran pretreatment antagonizes CPF induced lipid peroxidative damage,the mechanism may be related to that carbofuran induces slightly oxidative stress and increases the anti-oxidative enzymes activity.
Conclusion:
1.Noncytotoxic concentration of CPF can induce tolerance of hippocampal neurons,and induces cytotoxicity after withdrawal,while ERK inhibition and cholinergic deficit are related to the mechanism of CPF withdrawal induced cytotoxicity,suggesting OPICN be related to withdrawal symptom.
2.Carbofuran pretreatment can antagonize cytotoxicity induced by chlopyrifos in neronal cells,with the mechansim involving that carbofuran pretreatment reduces ERK1/2 activation and oxidative stress induced by CPF,suggesting the mode of combined action is affected by the exposure interval between the two pesticides.
引文
[1]Lange W,von Krueger G.Uber ester der Monofluorphosphorsaure.Ber Dtsch Chem Ges.1932,65:1598-1601.
[2]Schrader G.Organische Phosphor-Uerbindungenals neurartige Insekticide(Auszug).Angew Chem.1950,62:471-473.
[3]Khurana D,Prabhakar S.Organophosphorus intoxication.Arch Neurol,2000,57:600-602.
[4]Metcalf RL.Structure-activity relationships for insecticidal carbamates.Bull Org Mond Sante Bull Wld Hlth Org.1971,44:43-78.
[5]夏世均主编,农药毒理学.化学工业出版社,2008,266-306.
[6]Machemer LH,Pickel M.Carbamte insecticide.Toxicol,1994,91:29-36.
[7]Bardin PG,Van Eeden SF,Moolman JA,et al.Organophosphate and carbamate poisoning.Arch Intem Med,1994,154:1433-1441.
[8]Prall YG,Gambhir KK,Ampy FR.Acetylcolinesterase:an enzymatic marker of human red blood cell aging.Life Sci,1998,63(3):177-186.
[9]李淮安,程爱国.血清胆碱酯酶临床研究进展.中国煤炭工业医学杂志,2008,11(1):119-121.
[10]Schuftz PG.The interplay between chemistry and biology in the design of enzymatic catalysts.Science,1988,240:426-432.
[11]何庆,万智,唐伦先.有机磷中毒救治与预防的重大进步—PON1研究进展.中华急诊医学杂志,2003,12(6):425-426.
[12]Furlong CE,Cole TB,Jarvik GP,et al.Pharmacogenomic considerations of the paraoxonase polymorphisms.Pharmacogenomics,2002,3:341-348.
[13]Valabhji J,Mccoll AJ,et al.High density lipoprotein tomposition and paraoxonase activity in Type Ⅰ diabetes.Clin Sci,2001,101:659-670.
[14]Costa LG,Cole TB,Jarvik GP,et al.Functional genomics of the paraoxonase(PON1)polymorphisms:efiects on pesticidesensitivity,cardiovascular disease,and drug metabolism.Annu Rev Med,2003,54:371-392.
[15]Brophy VH,Jarvik GP,Richter RJ,et al.Analysis of paraoxonase(PON1) L55M status requires both genotype and phenotype.Pharmacogengetics,2000,10:453-460.
[16]Furlong CE.PON1 status and neurologic symptom complexes in Gulf War veterans.Genome Res,2000,10:153-155.
[17]陈曙旸,王鸿飞.1992-1996年我国农村农药中毒报告发病情况.农药科学与管理,1997,18(4): 40-43.
[18]Sloviter RS,Dempster DW.'Epileptic' brain damage is replicated qualitatively in the rat hippocampus by central injection of glutamate or asparate but not by GABA or acetylcholine.Brain Res Bull,1985,15:39-60.
[19]王汉斌,张晋,赵赞梅.有机磷化合物致中枢神经系统损伤机制研究进展 世界危重病医学杂志,2005,2(3)726-728.
[20]Yang CC,Deng JF.Intermediate syndrome following organophosphate insecticide poisoning.J Chin Med Assoc,2007,70(11):467-472.
[21]De Bleecker J,Vanden Neucker K,Colardyn F.Intermediate syndrome in organophosphorus poisoning:a prospective study.Crit Care Med,1993,21:1706-1711.
[22]王芳,姚林,王广增.有机磷农药中毒致神经损伤机制的研究进展华北煤炭医学院学报,2005,7(2):159-161.
[23]梁松健.有机磷中毒与中间综合征.中华现代内科学杂志,2005,2(8):675
[24]张随玉.急性有机磷农药中毒后高血钠发生的危险因素及预后.中国误诊学杂志,2003,3(2):213-214.
[25]何军山,卢新华,曹慧芳,等.有机磷农药中毒对小鼠糖代谢影响的实验研究.实用预防医学,2003,10(1):21-22.
[26]郑荣远.甲胺磷中毒迟发多发性神经病的临床特征.中华内科杂志,1990,29(2):79
[27]孙东汇,薛寿征,周宏东,等.甲胺磷经口中毒者后遗迟发性多发性神经病变的调查研究.职业医学,1994,21(2):15-18.
[28]Johnson MK.Symposium introduction:retrospect and prospects for neuropathy target esterase (NTE) and the delayed polyneuropathy(OPIDP) induced by some organophorus esterase.Chem-Biol Interactions,1993,87:339-415.
[29]ECETOC.Organophosphorus pesticides and long-term effects on the nervous system[M].Brussesl,1998,11-17.
[30]郑荣远.甲胺磷中毒迟发多发性神经病的临床特征.中华内科杂志,1990,29(2):79.
[31]Abou-Donia MB.Involvement of cytoskeletal proteins in the mechanisms of organophosphorus ester-induced delayed neurotoxicity.Clin Exp Pharmacal,1995,22:358-359.
[32]王汉斌,阮金秀.急性有机磷农药中毒致脏器损害与并发症的防治.中华急诊医学杂志,2001,10(4):285-287.
[33]Ali FA,Abdalla MH.Pathological in testes and liver of male albino rats after dermal exposure to DDVP insecticide.J Egypt Public Health Assoc,1992,67:565-578.
[34]刘华盛.急性有机磷农药中毒中间综合征9例报告.广西医科大学学报,2000,17(1):147-148.
[35]刘勇,何彩平.有机磷毒剂心脏毒性的实验研究进展,中国工业医学杂与,2000,13(6):364-365.
[36]孟侠.重度有机磷农药中毒的心肌损害.伤残医学杂志,1995,10(13):593.
[37]Nguyena TD,Maquartb FX,Monboisse JC.Ionizing radiations and collagen metabolism:from oxygen free radicals to radio-induced late fibrosis.Radia Physics and Chem,2005,72:381-386.
[38]Leonard SS,Harris GK,Shi X.Metal-induced oxidative stress and signal transduction.Free Rad Biol Med,2004,37:1921-1942.
[39]Freitas I,Griffini P,Bertone V,et al.In situ detection of reactive oxygen species and nitric oxide production in normal and pathological tissues:improvement by differential interference contrast.Exper Gerontol,2002,37:591-602.
[40]Banerjee BD,Bhattacharya A,Pasha ST.Biochemical effects of some pesticides on lipid peroxidation and free-radical scavengers.Toxicology Letters,1999,107:33-47.
[41]Ranjbar A,Pasalar P,Abdollahi M.2002.Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers.Human & Experimental Toxicology 21(4):179-182.
[42]Qiao D,Seidler FJ,Slotkin TA.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicol Appl Pharmacol,2005,206:17-26.
[43]Tuzmen N,Candan N,Kaya E,et al.2008.Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver.Cell Biochem Funct,26(1):119-124.
[44]Zhou JF,Xu GB,Fang WJ.Relationship between acute organophosphorus pesticide poisioning and damages induced by free radicals.Biomed Environ Sci,2002,15:177-186.
[45]Levins RS,Doull J.Global estimates of acute pesticide morbidity and mortality.Rev Environ Contamin Toxicol,1992,129:29-50.
[46]Barnes SM and Denz FA.The Reduction of Rats to Diets Containing Octamethyl Pyrophosphoramide(Schraden) and O,O-diethyl-5-ethylmercaptethanolthio-phospha(tesy stox) Br.J.Industr.Med.,1954,11:11-19.
[47]Rider JA,Eillineood LW,and Coon JM.Production of Tolerance in the Rat to Octamethyl (OMPA),Proc Soc Exp Biol Med.1952,81:455-459.
[48]Brodeur J,Dubois KP.Studies on the mechanism of acquired tolerance by O,O-diethyl S-2(ethylthio) phosphorodithioate (Di-Syston).Arch Int Pharmacodyn,1964,149:560-570.
[49]孙运光．有机磷农药所致耐受的研究进展．国外医学卫生学分册,200128(6)：325-329．
[50]Fitzgerald BB,Costa LG.Medulation of M_1 an d M_2 muscarinic receptor subtypes following repeated organ ophosphate exposure in rats.Toxicol Appl Pharmacol,1992,117:122-125.
[51]Stevens JT,Stitzel RE,McPhillips JJ.The effects of subacute administration of anticholinesterase insecticides on hepatic microsomal metabolism.Life Sci,1972,11:423-31.
[52]Gershon S,Shaw FB.Psychiatric sequelae of chronic exposure to organophosphate insecticides.Lancet,1961,1:1371-1374.
[53]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Arch Environ Health,2003,58:484-497.
[54]Alavanja MC,Hoppin JA,Kamel F.Health effects of chronic pesticide exposure:cancer and neurotoxicity.Annu Rev Public Health,2004,25:155-197.
[55]Ray DE.Chronic effects of low level exposure to anticholinesterases-a mechanistic review.Toxicology Letters,1998,103:527-533.
[56]Roldan-Tapia L,Leyva A,Laynez F,et al.Chronic neuropsychological sequelae of cholinesterase inhibitors in the Absence of structural brain damage:two cases of acute poisoning.Environ.Health Perspect,2005,113(6):762-766.
[57]Terry AV Jr,Gearhart DA,Beck WD Jr,et al.Chronic,intermittent exposure to chlorpyrifos in rats:protracted effects on axonal transport,neurotrophin receptors,cholinergic markers,and information processing.J Pharmacol Exp Ther,2007,322(3):1117-1128
[58]Savage EP,Keefe TJ,Mounce LM,et al.Chronic neurological sequelae of acute organophosphate pesticide poisoning.Arch Environ Health,1988,43:38-45.
[59]Rosenstock L,Keifer M,Daniell W,et al.Chronic central nervous system effects of acute organophosphate pesticide intoxication.Lancet,1991,338:223-227.
[60]Wesseling C,Keifer M,Ahlborn A,et al.Long-term neurobehavioral effects of mild poisoning with organophosphate and N-methyl carbamate pesticides among banana workers.Int J Occup Health,2002,8:27-34.
[61]Kamel F and Hoppin JA.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[62]Stephens R,Spurgeon A,Calvert IA,et al.Neuropsychological effects of long-term exposure to organophosphates in sheep dippers.Lancet 1995,345:1135-1139.
[63]Bazylewicz-Walczak B,Majczakowa W.Szymczak M.Behavioral effects of occupatio-nal exposure to organophosphorous pesticides in female greenhouse planting workers.Neurotoxicology,1999,20:819-826.
[64]Prendergast MA,Terry AV,Buccafusco JJ.Effects of chronic,low-level organophosp-hate exposure on delayed recall,discrimination,and spatial learning in monkeys and rats.Neurotoxicol Teratol,1998,20:115-122.
[65]Canadas F,Cardona D,Davila E,et al.Long-term neurotoxicity of chlorpyrifos:spatial learning impairment on repeated acquisition in a water maze.Toxicol Sci,2005,85:944-951.
[66]Sanchez-Santed F,Canadas F,Flores P,Lopez-Grancha M,Cardona D.Long-term functional neurotoxicity of paraoxon and chlorpyrifos:behavioural and pharmacological evidence.Neurotoxicol Teratol,2004,26:305-317.
[67]Duffy FH and Burchfield JL.Long term effects of the organophosphate sarin on EEGs in monkeys and humans.Neurotoxicology,1980,1:667-689.
[68]Song X,Seidler FJ,Saleh JL,et al.Cellular mechanisms for developmental toxicity of chlorpyrifos:targeting the adenylyl cyclase signaling cascade.Toxicol Appl Pharmaco,1997,145:158-174.
[69]Prendergast MA,Terry AV,Buccafusco JJ.Chronic,low-level exposure to diisopropylflu- rophosphate causes protracted impairment of spatial navigation learning.Psychopharmacology (Berl),1997,129:183-191.
[70]Schmuck G,Mihail F.Effects of the carbamates fenoxycarb,propamocarb and propoxur on energy supply,glucose utilization and SH-groups in neurons.Arch Toxicol,2004,78:330-337.
[71]Guillette EA,Meza MM,Aquilar MG,et al.An anthropological approach to the evaluation of preschool children exposed to pesticides in Mexico.Environ.Health Perspect,1998,106:347-353.
[72]Rohlman DS,Arcury TA,Quandt SA,et al.Neurobehavioral performance in preschool children from agricultural and non-agricultural communities in Oregon and North Carolina.Neurotoxicology,2005,26:589-98.
[73]Grandjean P,Harari R,Barr DB,et al.Pesticide exposure and stunting as independent predictors of neurobehavioral deficits in Ecuadorian school children.Pediatrics,2006,117:546-56.
[74]Ruckart PZ,Kakolewski K,Bove FJ,et al.Long-term neurobehavioral health effects of methyl parathion exposure in children in Mississippi and Ohio.Environ Health Perspect,2004,112:46-51.
[75]Patricia Sanchez Lizardi,Mary Kay O'Rourke,Richard J.Morris.The Effects of Organophosphate Pesticide Exposure on Hispanic Children's Cognitive and Behavioral Functioning.J Pediatr Psychol,2008,33:91-101.
[76]Young JG,Eskenazi B,Gladstone EA,et al.Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates.Neurotoxicology.2005,26:199-209.
[77]Whyatt RM,Rauh V,Barr DB,et al.Prenatal insecticide exposures and birth weight and length among an urban minority cohort.Environ Health Perspect,2004,112:1125-1132.
[78]U.S.Environmental Protection Agency.Administrator's Announcement.http://www.epa.gov/ pesticides/announcement 6800.htm,accessed 11 October 2000.
[79]Kurtz J.Dissociated behavioural and cholinesterase decrements following malathion exposure.Toxicol Appl Pharmacol,1977,42:589-594.
[80]Levin ED,Addy N,Nakajima A,et al.Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats.Dev Brain Res.2001,130:83-89.
[81]Crowder LA,Lanzaro GC,Whitson RS.Behavioral effects of methyl parathion and toxaphene exposure in rats.J Environ Sci Health B,1980,15:365-378.
[82]Aldridge JE,Levin ED,Seidler FJ,et al.Developmental Exposure of Rats to Chlorpyrifos Leads to Behavioral Alterations in Adulthood,Involving Serotonergic Mechanisms and Resembling Animal Models of Depression.Environ Health Perspect,2005,113:527-531.
[83]Stamper CR,Balduini W,Murphy SD,et al.Behavioral and biochemical effects of postnatal parathion exposure in the rat.Neurotoxicol Teratol,1988,10:261-266.
[84]Icenogle LM,Christopher NC,Blackwelder WP,et al.Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation.Neuroioxicol Teratol,2004,26:95-101.
[85]Roy TS,Seidler FJ,Slotkin TA:Morphologic effects of subtoxic neonatal chlorpyrifos exposure in developing rat brain:regionally selective alterations in neurons and glia.Brain Res Dev Brain Res,2004,148:197-206.
[86]Santos HR,Cintra WM,Aracava Y.Pine density and dendritic branching pattern of hippocampal CA1 pyramidal neurons in neonatal rats chronically exposed to the organophosphate paraoxon.Albuquerque Neurotoxicology,2004,25:481-494.
[87]Lassiter T,Brone S.Gestational exposure to chlopyrifos:qualitative and quantitative neuropathological changes in the fetal neocortex.Toxicologist,2002,66:632-53.
[88]Qiao D,Seidier FJ,Abreu-Villaca Y,et al.Chlorpyrifos exposure during neurulation:cholinergic synaptic,dysfunction and cellular alterations in brain regions at adolescence and adulthood.Dev Brain Res.2004,148:43-52.
[89]Dam K,Seidier FJ.Slotkin TA,et al.Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity.Brain Res Dev Brain Res,2000,121:179-187.
[90]Rice D,Barone S,Jr.Critical periods of vulnerability for the developing nervous system:evidence from humans and animal models.Environ.Health Perspect,2000,108:511-533.
[91]HunterDL,LassiterTL,Padilla S.Gestational exposure to chlorpyrifos:comparative distribution of trichloropyridinol in the fetus and dam.Toxicol Appl Pharmacol,1999,158:16-23.
[92]Pope CN,Chakraborti TK,Chapman ML,et al.Comparison of in vivo cholinesterase inhibition in neonatal and adult rats by three organophosphorothioate insecticides.Toxicology,1991,68:51-61.
[93]Chanda SM,Harp P,Liu J.et al.Comparative developmental and maternal neurotoxicity following acute gestational exposure to chlorpyrifos in rats.J Toxicol Environ Health,1995,44:189-202.
[94]Chanda SM,Pope CN.Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats.Pharmacol Biochem Behav,1996,53:771-776.
[95]Lassiter TL,Padilla S,Mortensen SR,et al.Gestational exposure to chlorpyrifos:apparent protection of the fetus? Toxicol Appl Pharmacol.1998,152:56-65.
[96]Atterberry TT,Burnett WT,Chambers JE.Age-related differences in parathion and chlorpyrifos toxicity in male rats:target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism.Toxicol.Appl.Pharmacol,1997,147:411-418.
[97]Slotkin TA.Cholinergic systems in brain development and disruption by neurotoxicants:nicotine,environmental tobacco smoke,organophosphates.Toxicol Appl Pharmacol,2004,198(2):132-151.
[98]Whitney KD,Seidier FJ,Slotkin TA.Developmental neurotoxicity of chlorpyrifos:cellular mechanisms.Toxicol Appl Pharmacol,1995,134:53-62.
[99]Qiao D,Seidier FJ,Slotkin TA.Developmental neurotoxicity of chlorpyrifos modeled in vitro:comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC 12 and C6 cells.Environ Health Perspect,2001,109:909-913.
[100]Zheng T,Zahm SH,Cantor KP,Weisenburger DD,Zhang Y,Blair A.Agricultural exposure to carbamate pesticides and risk of non-Hodgkin lymphoma.J Occup Environ Med,2001,43(7):641-649.
[101]Blair A,Zahm SH.Agricultural exposures and cancer.Environ Health Perspect,1995,103:205-208.
[102]Gurney JG,Smith MA,Olshan AF,et al.Clues to the etiology of childhood brain cancer:N-nitroso compounds,polyomaviruses,and other factors of interest.Cancer Invest,2001,19:630-640.
[103]Efird JT,Holly EA,Preston-Martin S,et al.Farm-related exposures and childhood brain tumours in seven countries:results from the SEARCH International Brain Tumour Study.Paediatr Perinat Epidemiol,2003,17:201-211.
[104]Daniels JL,Olshan A F,Savitz DA.Pesticides and childhood cancers.Environ Health Perspect,1997,105:1068-1077.
[105]世界资源研究所,联合国环境规划署,联合国开发计划署等编.世界资源报告—环境变化与人体健康(1998-1999).北京:中国环境科学出版社,1999.3.
[106]Colborn T.Endocrine disruption from environmental toxicant.In:Rom WN,ed.Environmental and Occupational Medicine,3rd ed.Philadelphia:Lippincott-Raven Publishers,1998.
[107]Andrea CG.Environmental toxicant effects on neuroendocrine function.Endocrine,2001,14:235-246.
[108]Padungtod C,Lasley BL,Christiani DC,et al.Reproductive hormone profile along pesticide factory workers.J Occup Env Med,1998,40:1038-1047.
[109]詹宁育,王心如,王沭沂,等.辛硫磷育氰戊菊酯对大鼠睾丸的联合毒性作用.中华劳动卫生职业病杂志.2001,19(4):261-264.
[110]王捷,朱宏宇,胡翠清.农药生殖毒性的回顾.农药,2005,44(11):489-505.
[111]刘学,李贤相,江隆久,等.U-Cell法测定农药对男性精子机能影响的分析.疾病控制与防治杂志,1999,3(2):84-87.
[112]Recio R,Robbins WA,Borja-Aburto V,et al.Organophosphorous pesticide exposure increases the frequency of sperm sex null aneuploidy.Environ Health Perspect,2001,109:1237-1040.
[113]Padungtod C,Lasley BL,Christiani DC,et al.Reproductive hormone profile among pesticide factory workers.J Occup Environ Med,1998,40:1038-1047
[114]张霜红,王锦珍,王治明.职业性农药接触对女工生殖功能的影响.现代预防医学,2004,31(5):664-665.
[115]Chia SE,Shi LM.Review of recent epidemiological studies on patemal occupations and birth defects.Occupational and Environmental Medicine,2002,59(3):149-155.
[116]罗永有.我国出生缺陷干预现状与发展趋势.实用预防医学,2005,12(2):458-461.
[117]刘守庆,石宝增.临沂市某农药厂环境染染与新生儿出生缺陷的流行病学调查研究.预防医学文献信息,2002,8(3):273-274.
[118]Shaw GM,Wasserman CR,O'Malley CD,et al.Maternal pesticide exposure from multiple sources and selected congenital anomalies.Epidemiology,1999,10:60-62.
[119]Karanth S.OLiver K,Liu J,et al.In vivo interaction between chlorpyrifos and parathion in adult rats:sequence of administration can markedly influence toxic outcome.TOxicol Appl Pharmacol,2001,177:247-255.
[120]何凤生,陈署旸.混配农药中毒的防治研究.中华医学信息导报,2002,11:16-17.
[121]欧阳明,林雪梅,盛书样,等.评价杀虫剂混用联合作用的六种方法比较.农药科学与管理,1997,18(1):20-29.
[122]Large P,Wiezorek WD.The effects of diethyldithiocarbamate on the acute toxicity and the acetylcholinesterase inhihition by methylparathion in mice.Acta Biol Med Germ,1975,34(2):427-433.
[123]Hayes WJ,Laws ER.Handbook of pesticide toxicology.New York:San Francisco Academic Ptess,1991,2:588
[124]Mansour NA,Eldefrawi ME,Toppodaza A,et al.Toxicological studies on the Egyptian cotton leafworm,prodenia litura.Ⅵ.potentiation and antagonism of organophosphorus and carbamate insecticides.J Eco Entomol.1966,59(2):307-311.
[125]Petroianu GA,Nurulain SM,Ararat K,et al.Effect of pyridostigmine,pralidoxime and their combination on sarvival and cholinesterase activity in rats exposed to the organophosphate paraoxon.Arch Toxicol.2006,80(11):777-784.
[126]Eckert S,Eyer P,Mückter H,et al.Kinetic analysis of the protection afforded by reversible inhibitors against irreversible inhibition of acetylcholinesterase by highly toxic organophosphorus compounds.Biochem Pharmacol,2006,72(3):344-357.
[127]Keplinger ML,Deichmann WB.Acute toxicity of combinations of pesticides.Toxicol Appl Pharmacol,1967,10(3):586-598.
[128]Sultatos LG,Murphy SD.Kinetic analysis of the microsomal biotransmation of the phosphorothioate insecticides chlorpyrifos and parathion.Fundan Appl Toxicol,1983,3(1):16-21
[129]孙金秀,陈波,姚佩佩.农药混剂联合毒性评价.卫生研究,2000,29(2):65-68.
[130]颜冬云,蒋新,余贵芬,等.有机磷农药对乙酰胆碱酯酶活性的联合抑制作用.农药,2006,45(1):31-34.
[1]Wesseling C,Keifer M.Ahlborn A,McConeel R,Moon J,Risenstock L,et al.Long-term neurobehavioral effects of mild poisoning with organophosphate and N-methyl carbamate pesticides among banana workers.Int J Occup Health,2002,8:27-34.
[2]Jamal GA.Neurological syndromes of organophosphorus compounds.Adverse Drug React Toxicol Rev,1997,16:133-170.
[3]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Arch Environ Health,2003,58:484-497.
[4]Ahmed GM and Davies DR.Chronic organophosphate exposure:towards the definition of a neuropsychiatric syndrome.J Nutr Environ Med,1997,7:169-176.
[5]Colosio C,Tiramani M,Maroni M.Neurobehavioral effects of pesticides:state of the art.Neurotoxicology,2003,24:577-591.
[6]Gershon S and Shaw FB.Psychiatric sequelae of chronic exposure to organophosphate insecticides.Lancet,1961,1:1371-1374.
[7]Metcalf DR,Holmes JH.EEG,Psychological and neurological alterations in human with organophosphorus exposure.Ann NY Acad Sci,1969,160:357-365
[8]Savage EP,Keefe TJ,Mounce LM.Heaton RK,Lewis JA,Burcar PJ.Chronic neurological sequelae of acute organophosphate pesticide poisoning.Arch Environ Health,1988.43:38-45.
[9]Rosenstock L,Keifer M,Daniell W,McConnell R,Claypoole K.Chronic central nervous system effects of acute organophosphate pesticide intoxication.Lancet,1991,338:223-227.
[10]Jamal GA and Julu P.Low level exposures to organophosphorus esters may cause neurotoxicity.Toxicology,2002,181:23-33.
[11]Kamel F and Hoppin JA.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[12]Stephens R,Spurgeon A,Calvert IA,Beach J,Levy LS,Berry H,et al.Neuropsychological effects of long-term exposure to organophosphates in sheep dippers.Lancet,1995,345:1135-1139
[13]Bazylewicz-Walczak B,Majczakowa W,Szymczak M.Behavioral effects of occupational exposure to organophosphorous pesticides in female greenhouse planting workers.Neurotoxicology,1999,20:819-826.
[14]Prendergast MA,Terry AV,Buccafusco JJ.Effects of chronic,low-level organophosphate exposure on delayed recall,discrimination,and spatial learning in monkeys and rats.Neurotoxicol Teratol,1998,20:115-122.
[15]Kassa J,Koupilova M,Vachek J.The influence of low-level sarin inhalation exposure on spatial memory in rats.Pharmacol Biochem Behav,2001,70:175-179.
[16]Canadas F,Cardona D,D(?)vila E,Sanchez-Santed F.Long-term neurotoxicity of chlorpyrifos:spatial learning impairment on repeated acquisition in a water maze.Toxicol Sci,2005,85:944-951.
[17]Sanchez-Santed F,Ca(?)adas F,Flores P,L(?)pez-Grancha M,Cardona D.Long-term functional neurotoxicity of paraoxon and chlorpyrifos:behavioural and pharmacological evidence.Neurotoxicol Teratol,2004,26:305-317.
[18]Duffy FH and Burchfield JL.Long term effects of the organophosphate sarin on EEGs in monkeys and humans.Neurotoxicology,1980,1:667-689.
[19]Song X,Seidler FJ,Saleh JL,Zhang J,Padilla S,Slotkin TA.Cellular mechanisms for developmental toxicity of chlorpyrifos:targeting the adenylyl cyclase signaling cascade.Toxicol Appl Pharmaco,1997,145:158-174.
[20]Prendergast MA,Terry AV,Buccafusco JJ.Chronic,low-level exposure to diisopropylfluorophosphate causes protracted impairment of spatial navigation learning.Psychopharmacology (Berl),1997.129:183-91.
[21]Schmuck G and Mihail F.Effects of the carbamates fenoxycarb,propamocarb and propoxur on energy supply,glucose utilization and SH-groups in neurons.Arch Toxicol,2004,78:330-337.
[22]Terry AV,Stone JD,Buccafusco JJ,Sickles DW,Sood A,Prendergast MA.Repeated exposures to subthreshold doses of chlorpyrifos in rats:hippocampal damage,impaired axonal transport,and deficits in spatial learning.J Pharmacol Exp Ther,2003,305:375-384.
[23]Goekoop R,Scheltens P,Barkhof F,Rombouts S.Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation—a pharmacological fMRI study.Brain,2006,129:141-157.
[24]Eichenbaum H.Hippocampus cognitive processes and neural representations that underlie declarative memory.Neuron,2004,44:109-120.
[25]Gron G,Brandenburg I,Wunderlich AP,Riepe MW.Inhibition of hippocampal function in mild cognitive impairment:targeting the cholinergic hypothesis.Neurobio Aging,2006,27:78-87.
[26]Zhang M,Wang A,He W,et al.Effects of fluoride on the expression of NCAM,oxidative stress,and apoptosis in primary cultured hippocampal neurons.Toxicology,2007,236:208-216.
[27]Harkins J,Arsenault M,Schlesinger K,et al.Induction of neuronal functions:acetylcholine-induced acetylcholinesterase activity in mouse neuroblastoma cells.Proc Nat Acad Sci USA,1972,69 (11):3161-3164.
[28]Mosmann T.Rapid colorimetric assay for cellular growth and survival:application to proliferation and neurotoxicity assays.J Immunol Methods,1983,65:55-63.
[29]Schengrund C and Marangos P.Neuron-specific enolase levels in primary cultures of neurons.J Neurosci,2004,5:305-311.
[30]Wang W,Iyo A,Miguel-Hidalgoa J,Regunathana S,Zhu M.Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons.Brain Res,2006,1084:210-216.
[31]Rosenblum K,Futter M,Jones M,Hulme EC,Bliss TV.ERK1/2 regulation by the muscarinic acetylcholine receptors in neurons.J Neurosci,2000,20:977-985.
[32]Yan GM,Lin SZ,Irwin RP,Paul SM.Activation of muscarinic cholinergic receptors blocks apoptosis of cultured cerebellar granule neurons.Mol Pharmacol,1995,47:248-257.
[33]Caughlan C,Newhous K,Namgung UK,Xia Z.Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases.Toxicol Sci,2004,78:125-134.
[34]Robinson MJ and Cobb MH.Mitogen-activated protein kinase pathways.Curr Opin Cell Biol,1997,9:180-186.
[35]Atkins CM,Selcher JC,Petraitis JJ.trzaskos JM,Sweatt JD.The MAPK cascade is required for mammalian associative learning.Nature Neurosci,1998,1:602-609.
[36]Xia Z,Dickens M,Raingeaud J,Davis RJ,Greenberg ME.Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.Science,1995,270:1326-1331
[37]Hetman M,Kanning K,Cavanaugh JE,Xia Z.Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol-3 kinase.J Biol Chem,1999,274:22569-22580.
[38]Singer CA,Figueroa-Masot XA,Batchelor RH,Dorsa DM.The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons.J Neurosci,1999,19:2455-63.
[39]Szatmari E,Katarzyna B,Kalita,Kharebava G,Hetman M.Role of kinase suppressor of ras-1 in neuronal survival signaling by extracellular signal-regulated kinase 1/2.J Neurosci,2007,27:11389-11400.
[40]Araki W and Wurtman RJ.Increased expression of amyloid precursor protein and amyloid precursor-like protein 2 during trophic factor withdrawal-induced death of neuronal PC 12 cells.Mol Brain Res,1998,56:169-177.
[41]Murray B,Alessandrini A.Cole A,Yee A,Furshpan E.Inhibition of the ERKl/2 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity.Proc Natl Acad Sci USA,1998,95:11975-11980.
[42]Alessandrini A,Namura S,Moskowitz MA,Bonventre JV.MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia.Proc Natl Acad Sci USA,1999,96:12866-12869.
[43]Stanciu M,Wang Y,Kentor R,Burke N,Watkins S,Kress G,et al.Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures.J Biol Chem,2000,275:12200-12206.
[44]Fukunaga K and Miyamoto E,1998,Mol Neurobiol 16:79-95.
[45]Takagi N,Miyake-Takagi K,Takagi K,Tamura H,Takeo S.Altered extracellular signal-regulated kinase signal transduction by the muscarinic acetylcholine and metabotropic glutamate receptors after cerebral ischemia.J Biol Chem,2002.277:6382-6390.
[46]Thoenen H.Neurotrophins and neuronal plasticity.Science,1995,270:593-598.
[47]Bowden CA,Krenzelok EP.Clinical applications of commonly used contemporary antidotes.A US perspective.Drug Saf,1997.16:9-47.
[48]Alessi DA,Cuenda A,Cohen P,Dudley DT,Saltiel AR.PD98059 is a specific inhibitor of the activation of mitogen activated protein kinase in vitro and in vivo.J Biol Chem,1995,270:27489-27494.
[49]Jameson RR,Seidler FJ,Slotkin TA.Nonenzymatic functions of acetylcholinesterase splice variants in the developmental neurotoxicity of organophosphates:chlorpyrifos,chlorpyrifos oxon,and diazinon.Environ Health Perspect,2007,115:65-70.
[50]Das KP and Barone S Jr.Neuronal differentiation in PC 12 cells is inhibited by chlorpyrifos and its metabolites:Is acetylcholinesterase inhibition the site of action? Toxicol Appl Pharmacol.1999,160:217-230.
[51]Kaneko N,Okano H,Sawamoto K.Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb.Genes Cells,2006,11: 1145-1159.
[52]Yan GM,Lin SZ,Irwin RP,Paul SM.Activation of muscarinic cholinergic receptors blocks apoptosis of cultured cerebellar granule neurons.Mol Pharmacol,1995,47:248-257.
[53]White J.Pleasure into pain:the consequences of long-term opioid use.Addict Behav,2004,29:1311-1324.
[54]Hochberg Z,Pacak K,Chrousos G.Endocrine withdrawal syndromes.Endocr Rev,2003,24:523-538.
[55]Russell RW,Overstreet DH,Cotman CW,Carson VG,Churchill L,Dalglish FW,et al.Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase,diisopropyl fluorophosphate.J Pharmacol Exp Ther,1975,192:73-85.
[56]Schwab BW,Costa LG,Murphy SD.Muscarinic receptor alterations as a mechanism of anticholinesterase tolerance.Toxicol Appl Pharmacol,1983,71:14-23.
[57]Costa LG and Murphy SD.Unidirectional cross-tolerance between the carbamate insecticide Propoxur and the organophosphate Disulfoton in mice.Fundam Appl Toxicol,1983,3:483-488.
[58]Bushnell PJ,Kelly KL,Ward TR.Repeated inhibition of cholinesterase by chlorpyrifos in rats:behavioral,neurochemical and pharmacological indices of tolerance.J Pharmacol Exp Ther,1994,270:15-25.
[59]Slotkin TA,Cousins MM,Tate CA,Seidier FJ.Persistent cholinergic presynaptic deficits after neonatal chlorpyifos exposure.Brain Res,2001,902:229-243.
[60]Kaufer D,Friedman A,Seidman S,Soreq H.Anticholinesterases induce multigenic transcriptional feedback response suppressing cholinergic neurotransmission.Chem Biol Interact,1999,119:349-60.
[61]Liu J and Pope CN.Effects of chlorpyrifos on high-affinity choline uptake,and [~3H]hemicholinium-3 binding in rat brain.Fundam Appl Toxicol,1996,34:84-90.
[62]Plotkin DA and Jarvik LF.Cholinergic dysfunction in Alzheimer's disease:cause or effect? Prog Brain Res,1986,65:91-102.
[63]Schliebs R and Arendt T.The significance of the cholinergic system in the brain during aging and in Alzheimer's disease.J Neural Transm,2006,113:1625-1644.
[1]Hochberg Z,Pacak K.Chrousos G.Endocrine withdrawal syndromes.Endocr Rev,2003,24:523-538.
[2]White J.Pleasure into pain:the consequences of long-term opioid use.Addict Behav,2004,29:1311-1324.
[3]Zhang M,Wang A,He W,He P,Xu B,Xia T,et al.2007.Effects of fluoride on the expression of NCAM,oxidative stress,and apoptosis in primary cultured hippocampal neurons.Toxicology,236:208-216.
[4]Kamel F and Hoppin JA.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[5]Rosenstock L,Keifer M,Daniell W,McConnell R,Claypoole K.Chronic central nervous system effects of acute organophosphate pesticide intoxication.Lancet,1991,338:223-227.
[6]Barnes SM and Denz FA.The Reduction of Rats to Diets Containing Octamethyl Pyrophosphoramide (Schraden) and O,O-diethyl-5-ethylmercaptethanolthio-phospha(tesy stox) Br.J.Industr.Med.,1954,11:11-19.
[7]Rider JA,Eillineood LW,and Coon JM.Production of Tolerance in th e Rat to Octamethyl (OMPA),Proc Soc Exp Biol Med.1952,81:4 55-459.
[8]Nobuhiro Konno,Toru Yamauchi,Yasuaki Yamaguchi and Masaaki Fukushima.Protective effect of pretreatment against the acute toxicity of formulated cyanofenphos in hens.The Tohoku Journal of Experimental Medicine.1984,142(2):155-163.
[9]Bushnell PJ,Kelly KL,Ward TR.Repeated inhibition of cholinesterase by chlorpyrifos in rats:behavioral,neurochemical and pharmacological indices of tolerance.J Pharmacol Exp Ther.1994,270(1):15-25.
[10]Bushnell PJ,Padilla SS,Ward T,Pope CN,Olszyk VB.Behavioral and neurochemical changes in rats dosed repeatedly with diisopropylfluorophosphate.J Pharmacol Exp Ther.1991,256(2):741-50
[11]Bushnell PJ,Pope CN,Padilla S.Behavioral and neurochemical effects of acute chlorpyrifos in rats:tolerance to prolonged inhibition of cholinesterase.The Journal of pharmacology and experimental therapeutics.1993,266(2):1007-1017.
[12]Kornnika Khanobdee,Naiphinich Kotchabhakdi,Piyarat Govitrapong.Development of tolerance to monocrotophos.Thammasat Int J Sc.Tech.1999,4(1):61-67.
[13]Jeffrey Cohn and Robert C.Macphail.Chlorpyrifos produces selective learning deficits in rats working under a schedule of repeated acquisition and performance.J Pharmacol Exp Ther.1997,283(1):312-320.
[14]Luczak C,Gralewicz S,Górny R.Tblerance to chlorphenvinphos in rats assessed on the basis of changes in locomotor behavior in rotating wheels.Pol J Occup Med Environ Health.1992,5(1):43-54
[15]孙运光.有机磷农药所致耐受性的研究进展.国外医学卫生学分册,2001,28(6):325-329.
[16]Schwab BW,Costa LG,Murphy SD.Muscarinic receptor alterations as a mechanism of anticholinesterase tolerance.Toxicol Appl Pharmacol,1983,71:14-23.
[17]Fitzgerald BB,Costa LG.Medulation of M_1 and M_2 muscarinic receptor subtypesfollowing repeated organophosphate exposure in rats.Toxicol Appl Pharmacol,1992,117:122-125.
[18]孙运光,周志俊,胡云平.乐果亚急性染毒诱导大鼠耐受以及对大鼠脑组织M受体的影响,环境与职业医学,2003,20(3):154-158.
[19]伍一军,孙健英,鲍凯瑞.有机磷类杀虫剂对脑突触体烟碱型自主受体功能的影响.中华劳动卫生职业病杂志,2003,21(3):188-190.
[20]Gazit H,Silman I,and Dudai Y.Administration of an organophosphate causesa decrease in muscarinic receptor levels in rat brain.Brain Res.1979,174:315-356.
[21]Slotkin TA,Cousins MM,Tate CA,Seidler FJ.Persistent cholinergic presynaptic deficits after neonatal chlorpyifos exposure.Brain Res 2001,902(2):229-243.
[22]Jing Liu Carey N.Pope.Comparative presynaptic neurochemical changes in rat striatum following exposure to chlorpyrifos or parathion.J Toxicol Environ Health.1998,53(7):531-544.
[23]Ward TR,Mundy WR.Organophosphorus compounds preferentially affect second messenger systems conpled to M_2/M_4 receptors in rat frontal cortex.Brain Res Bull,1996,39:49-55.
[24]Russell RW,Overstreet DH,Cotrnan CW,Carson VG,Churchill L,Dalglish FW,VaLsquez BJ.Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase,diisopropylfluorophosphate.J Pharmacol Exp Ther,1975,192:73-85.
[1]杨霓云,刘征涛,王宏,等.五氯苯酚与邻氯苯酚和2,4-二氯苯酚对斑马鱼的联合毒性[J].环境科学研究,2006,19(6):145-148.
[2]杨永滨,刘征涛,郑明辉,等.卤代酚对斑马鱼的急性联合毒性效应研究.环境科学研究.2007,20(2):5-8.
[3]Boon P E,Van der Voet H,Van Raaij M T,et al.Cumulative risk assessment of the exposure to organophosphorus and carbamate insecticides in the Dutch diet.Food Chem Toxicol,2008,46:3090-3098.
[4]Rice P J,Rice P J,Arthur E L,et al.Advances in pesticide environmental fate and exposure assessments.J Agric Food Chem,2007,55(14):5367-5376.
[5]Boobis AR,Ossendorp BC,Banasiak U,et al.Cumulative risk assessment of pesticide residues in food.Toxicol Lett.2008,180(2):137-150.
[6]Jensen AF,Petersen A,Granby K,et al.Cumulative risk assessment of the intake of organophosphorus and carbamate pesticides in the Danish diet.Food Addit Contam.2003,20(8):776-785.
[7]文一,潘家荣.有机磷农药的联合毒性研究进展.环境与健康杂志,2007,24(7):553-555.
[8]孙金秀,陈波,姚佩佩.农药混剂联合毒性评价.卫生研究,2000,29(2):65-66.
[9]孔祥锋,陈婉蓉,倪兵,等.H_2O_2对大鼠神经细胞的氧化损伤及硒的保护作用.卫生毒理学杂志,2000,14(2):91-94.
[10]祁爱群,邱俭,肖林,等.糖皮质激素对原代培养的海马细胞中p44/42的快速非基因组激活作用.自然科学进展,2004,14(7):760-766.
[11]Caughlan A,Newhous K,Namgung U K,et al.Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases.Toxicol Sci,2004,78(1):125-134.
[12]Kamel F,Hoppin,J A.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[13]Petroianu G A,Nurulain S M,Arafat K,et al.Effect of pyridostigmine,pralidoxime and their combination on survival and cholinesterase activity in rats exposed to the organophosphate paraoxon.Arch Toxicol,2006,80(11):777-784.
[14]Golomb B A.Acetylcholinesterase inhibitors and Gulf War illnesses.Proc Natl Acad Sci USA,2008,105(11):4295-4300.
[15]Rosenblum K,Futter M,Jones M,et al.ERK1/2 regulation by the muscarinic acetylcholine receptors in neurons.J Neurosci,2000,20(3):977-985.
[16]Robinson M J and Cobb M H.Mitogen-activated protein kinase pathways.Curr Opin Cell Biol,1997,9:180-186.
[1]Nguyena TD,Maquartb FX,Monboisse JC.Ionizing radiations and collagen metabolism:from oxygen free radicals to radio-induced late fibrosis.Radia Physics and Chem,2005,72:381-386.
[2]Leonard SS,Harris GK,Shi X.Metal-induced oxidative stress and signal transduction.Free Rad Biol Med,2004,37:1921-1942.
[3]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Arch Environ Health,2003,58:484-497.
[4]Milatovic D,Gupta RC,Aschner M.Anticholinesterase toxicity and oxidative stress.Sci World J,2006,6:295-310.
[5]Dettbarn WD.Milatovic D.and Gupta RC.Oxidative stress in anticholinesterase-induced excitotoxicity.In:R.C.Gupta,Editor,Toxicology of Organophosphate and Carbamate Compounds,Academic Press/Elsevier,Amsterdam,2006,511-532.
[6]Esterbauer H,Cheeseman KH.Determination of aldehydic lipid peroxidation products:malonaldehyde and 4-hydroxynonenal.Methods Enzymol,1990,186:407-421.
[7]Spitz DR,Oberley LW.An assay for superoxide dismutase activity in mammalian tissue homogenates.Anal Biochem,1989,179:8-18.
[8]El-Missiry MA,Abou-Seif M.Photosensitization induced reactive oxygen species and oxidative damage in human erythrocytes.Cancer Lett,2000,158:155-163.
[9]Paglia DE,Valentine WN.Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.J Lab Clin Med,1967,70:158-170.
[10]Gupta RC,Milatovic S,Dettbarn WD,Aschner M,Milatovic D.Neuronal oxidative injury and dendritic damage induced by carbofuran:protection by memantine.Toxicol Appl Pharmacol,2007,219:97-105.
[11]Kamboj SS,Kumar V,Kamboj A,Sandhir R.Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran exposure.Cell Mol Neurobiol,2008,28:961-969.
[12]Rai DK,Sharma B.Carbofuran-induced oxidative stress in mammalian brain.Mol Biotechnol,2007,37:66-71.
[13]Kamboj A,Kiran R,Sandhir R.Carbofuran-induced neurochemical and neurobehavioral alterations in rats:attenuation by N-acetylcysteine.Exp Brain Res,2006,170:567-575.
[14]Shadnia S,Azizi E,Hosseini R,Khoei S,Fouladdel S,Pajoumand A,et al.Evaluation of oxidative stress and genotoxicity in organophosphorus insecticide formulators.Hum Exp Toxicol,2005,24(9): 439-445.
[15]Ranjbar A,Pasalar P,Abdollahi M.Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers.Hum Exp Toxicol,2002,21(4):179-182.
[16]Tuzmen N,Candan N,Kaya E,Demiryas N.Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver.Cell Biochem Funct,2008,26(1):119-124.
[17]Yu F,Wang Z,Ju B,Wang Y,Wang J,Bai D.Apoptotic effect of organophosphorus insecticide chlorpyrifos on mouse retina in vivo via oxidative stress and protection of combination of vitamins C and E.Exp Toxicol Pathol,2008,59(6):415-423.
[18]Slotkin TA,Oliver CA,Seidler FJ.Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline,alone or in combination.Brain Res Dev Brain Res,2005,157(2):172-180.
[19]Crumpton TL,Seidler FJ,Slotkin TA.Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos? Dev Brain Res.2000,121:189-195.
[20]Qiao D,Seidler FJ,Slotkin TA.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicol Appl Pharmacol,2005,206:17-26.
[21]Saulsbury MD,Heyliger SO,Wang K,Johnson DJ.Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells.Toxicology,2009.
[22]Giordano,G.,Afsharinejad,Z.,Guizzetti,M.,Vitalone,A.,Kavanagh,T.J.and Costa,L.G.Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency.Toxicol Appl Pharmacol,2007,219:181-189.
[23]Danielisova V,Nemethova M,Gottlieb M and Burdal J.Changes of endogenous antioxidant enzymes during ischemic tolerance acquisition.Neurochem Res,2005,30:559-565.
[24]Borrego A,Zamora ZB,Gonza'lez R,et al.Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats.Mediators Inflamm,2004,13:13-19.
[2]Schrader G.Organische Phosphor-Uerbindungenals neurartige Insekticide(Auszug).Angew Chem.1950,62:471-473.
[3]Khurana D,Prabhakar S.Organophosphorus intoxication.Arch Neurol,2000,57:600-602.
[4]Metcalf RL.Structure-activity relationships for insecticidal carbamates.Bull Org Mond Sante Bull Wld Hlth Org.1971,44:43-78.
[5]夏世均主编,农药毒理学.化学工业出版社,2008,266-306.
[6]Machemer LH,Pickel M.Carbamte insecticide.Toxicol,1994,91:29-36.
[7]Bardin PG,Van Eeden SF,Moolman JA,et al.Organophosphate and carbamate poisoning.Arch Intem Med,1994,154:1433-1441.
[8]Prall YG,Gambhir KK,Ampy FR.Acetylcolinesterase:an enzymatic marker of human red blood cell aging.Life Sci,1998,63(3):177-186.
[9]李淮安,程爱国.血清胆碱酯酶临床研究进展.中国煤炭工业医学杂志,2008,11(1):119-121.
[10]Schuftz PG.The interplay between chemistry and biology in the design of enzymatic catalysts.Science,1988,240:426-432.
[11]何庆,万智,唐伦先.有机磷中毒救治与预防的重大进步—PON1研究进展.中华急诊医学杂志,2003,12(6):425-426.
[12]Furlong CE,Cole TB,Jarvik GP,et al.Pharmacogenomic considerations of the paraoxonase polymorphisms.Pharmacogenomics,2002,3:341-348.
[13]Valabhji J,Mccoll AJ,et al.High density lipoprotein tomposition and paraoxonase activity in Type Ⅰ diabetes.Clin Sci,2001,101:659-670.
[14]Costa LG,Cole TB,Jarvik GP,et al.Functional genomics of the paraoxonase(PON1)polymorphisms:efiects on pesticidesensitivity,cardiovascular disease,and drug metabolism.Annu Rev Med,2003,54:371-392.
[15]Brophy VH,Jarvik GP,Richter RJ,et al.Analysis of paraoxonase(PON1) L55M status requires both genotype and phenotype.Pharmacogengetics,2000,10:453-460.
[16]Furlong CE.PON1 status and neurologic symptom complexes in Gulf War veterans.Genome Res,2000,10:153-155.
[17]陈曙旸,王鸿飞.1992-1996年我国农村农药中毒报告发病情况.农药科学与管理,1997,18(4): 40-43.
[18]Sloviter RS,Dempster DW.'Epileptic' brain damage is replicated qualitatively in the rat hippocampus by central injection of glutamate or asparate but not by GABA or acetylcholine.Brain Res Bull,1985,15:39-60.
[19]王汉斌,张晋,赵赞梅.有机磷化合物致中枢神经系统损伤机制研究进展 世界危重病医学杂志,2005,2(3)726-728.
[20]Yang CC,Deng JF.Intermediate syndrome following organophosphate insecticide poisoning.J Chin Med Assoc,2007,70(11):467-472.
[21]De Bleecker J,Vanden Neucker K,Colardyn F.Intermediate syndrome in organophosphorus poisoning:a prospective study.Crit Care Med,1993,21:1706-1711.
[22]王芳,姚林,王广增.有机磷农药中毒致神经损伤机制的研究进展华北煤炭医学院学报,2005,7(2):159-161.
[23]梁松健.有机磷中毒与中间综合征.中华现代内科学杂志,2005,2(8):675
[24]张随玉.急性有机磷农药中毒后高血钠发生的危险因素及预后.中国误诊学杂志,2003,3(2):213-214.
[25]何军山,卢新华,曹慧芳,等.有机磷农药中毒对小鼠糖代谢影响的实验研究.实用预防医学,2003,10(1):21-22.
[26]郑荣远.甲胺磷中毒迟发多发性神经病的临床特征.中华内科杂志,1990,29(2):79
[27]孙东汇,薛寿征,周宏东,等.甲胺磷经口中毒者后遗迟发性多发性神经病变的调查研究.职业医学,1994,21(2):15-18.
[28]Johnson MK.Symposium introduction:retrospect and prospects for neuropathy target esterase (NTE) and the delayed polyneuropathy(OPIDP) induced by some organophorus esterase.Chem-Biol Interactions,1993,87:339-415.
[29]ECETOC.Organophosphorus pesticides and long-term effects on the nervous system[M].Brussesl,1998,11-17.
[30]郑荣远.甲胺磷中毒迟发多发性神经病的临床特征.中华内科杂志,1990,29(2):79.
[31]Abou-Donia MB.Involvement of cytoskeletal proteins in the mechanisms of organophosphorus ester-induced delayed neurotoxicity.Clin Exp Pharmacal,1995,22:358-359.
[32]王汉斌,阮金秀.急性有机磷农药中毒致脏器损害与并发症的防治.中华急诊医学杂志,2001,10(4):285-287.
[33]Ali FA,Abdalla MH.Pathological in testes and liver of male albino rats after dermal exposure to DDVP insecticide.J Egypt Public Health Assoc,1992,67:565-578.
[34]刘华盛.急性有机磷农药中毒中间综合征9例报告.广西医科大学学报,2000,17(1):147-148.
[35]刘勇,何彩平.有机磷毒剂心脏毒性的实验研究进展,中国工业医学杂与,2000,13(6):364-365.
[36]孟侠.重度有机磷农药中毒的心肌损害.伤残医学杂志,1995,10(13):593.
[37]Nguyena TD,Maquartb FX,Monboisse JC.Ionizing radiations and collagen metabolism:from oxygen free radicals to radio-induced late fibrosis.Radia Physics and Chem,2005,72:381-386.
[38]Leonard SS,Harris GK,Shi X.Metal-induced oxidative stress and signal transduction.Free Rad Biol Med,2004,37:1921-1942.
[39]Freitas I,Griffini P,Bertone V,et al.In situ detection of reactive oxygen species and nitric oxide production in normal and pathological tissues:improvement by differential interference contrast.Exper Gerontol,2002,37:591-602.
[40]Banerjee BD,Bhattacharya A,Pasha ST.Biochemical effects of some pesticides on lipid peroxidation and free-radical scavengers.Toxicology Letters,1999,107:33-47.
[41]Ranjbar A,Pasalar P,Abdollahi M.2002.Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers.Human & Experimental Toxicology 21(4):179-182.
[42]Qiao D,Seidler FJ,Slotkin TA.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicol Appl Pharmacol,2005,206:17-26.
[43]Tuzmen N,Candan N,Kaya E,et al.2008.Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver.Cell Biochem Funct,26(1):119-124.
[44]Zhou JF,Xu GB,Fang WJ.Relationship between acute organophosphorus pesticide poisioning and damages induced by free radicals.Biomed Environ Sci,2002,15:177-186.
[45]Levins RS,Doull J.Global estimates of acute pesticide morbidity and mortality.Rev Environ Contamin Toxicol,1992,129:29-50.
[46]Barnes SM and Denz FA.The Reduction of Rats to Diets Containing Octamethyl Pyrophosphoramide(Schraden) and O,O-diethyl-5-ethylmercaptethanolthio-phospha(tesy stox) Br.J.Industr.Med.,1954,11:11-19.
[47]Rider JA,Eillineood LW,and Coon JM.Production of Tolerance in the Rat to Octamethyl (OMPA),Proc Soc Exp Biol Med.1952,81:455-459.
[48]Brodeur J,Dubois KP.Studies on the mechanism of acquired tolerance by O,O-diethyl S-2(ethylthio) phosphorodithioate (Di-Syston).Arch Int Pharmacodyn,1964,149:560-570.
[49]孙运光．有机磷农药所致耐受的研究进展．国外医学卫生学分册,200128(6)：325-329．
[50]Fitzgerald BB,Costa LG.Medulation of M_1 an d M_2 muscarinic receptor subtypes following repeated organ ophosphate exposure in rats.Toxicol Appl Pharmacol,1992,117:122-125.
[51]Stevens JT,Stitzel RE,McPhillips JJ.The effects of subacute administration of anticholinesterase insecticides on hepatic microsomal metabolism.Life Sci,1972,11:423-31.
[52]Gershon S,Shaw FB.Psychiatric sequelae of chronic exposure to organophosphate insecticides.Lancet,1961,1:1371-1374.
[53]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Arch Environ Health,2003,58:484-497.
[54]Alavanja MC,Hoppin JA,Kamel F.Health effects of chronic pesticide exposure:cancer and neurotoxicity.Annu Rev Public Health,2004,25:155-197.
[55]Ray DE.Chronic effects of low level exposure to anticholinesterases-a mechanistic review.Toxicology Letters,1998,103:527-533.
[56]Roldan-Tapia L,Leyva A,Laynez F,et al.Chronic neuropsychological sequelae of cholinesterase inhibitors in the Absence of structural brain damage:two cases of acute poisoning.Environ.Health Perspect,2005,113(6):762-766.
[57]Terry AV Jr,Gearhart DA,Beck WD Jr,et al.Chronic,intermittent exposure to chlorpyrifos in rats:protracted effects on axonal transport,neurotrophin receptors,cholinergic markers,and information processing.J Pharmacol Exp Ther,2007,322(3):1117-1128
[58]Savage EP,Keefe TJ,Mounce LM,et al.Chronic neurological sequelae of acute organophosphate pesticide poisoning.Arch Environ Health,1988,43:38-45.
[59]Rosenstock L,Keifer M,Daniell W,et al.Chronic central nervous system effects of acute organophosphate pesticide intoxication.Lancet,1991,338:223-227.
[60]Wesseling C,Keifer M,Ahlborn A,et al.Long-term neurobehavioral effects of mild poisoning with organophosphate and N-methyl carbamate pesticides among banana workers.Int J Occup Health,2002,8:27-34.
[61]Kamel F and Hoppin JA.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[62]Stephens R,Spurgeon A,Calvert IA,et al.Neuropsychological effects of long-term exposure to organophosphates in sheep dippers.Lancet 1995,345:1135-1139.
[63]Bazylewicz-Walczak B,Majczakowa W.Szymczak M.Behavioral effects of occupatio-nal exposure to organophosphorous pesticides in female greenhouse planting workers.Neurotoxicology,1999,20:819-826.
[64]Prendergast MA,Terry AV,Buccafusco JJ.Effects of chronic,low-level organophosp-hate exposure on delayed recall,discrimination,and spatial learning in monkeys and rats.Neurotoxicol Teratol,1998,20:115-122.
[65]Canadas F,Cardona D,Davila E,et al.Long-term neurotoxicity of chlorpyrifos:spatial learning impairment on repeated acquisition in a water maze.Toxicol Sci,2005,85:944-951.
[66]Sanchez-Santed F,Canadas F,Flores P,Lopez-Grancha M,Cardona D.Long-term functional neurotoxicity of paraoxon and chlorpyrifos:behavioural and pharmacological evidence.Neurotoxicol Teratol,2004,26:305-317.
[67]Duffy FH and Burchfield JL.Long term effects of the organophosphate sarin on EEGs in monkeys and humans.Neurotoxicology,1980,1:667-689.
[68]Song X,Seidler FJ,Saleh JL,et al.Cellular mechanisms for developmental toxicity of chlorpyrifos:targeting the adenylyl cyclase signaling cascade.Toxicol Appl Pharmaco,1997,145:158-174.
[69]Prendergast MA,Terry AV,Buccafusco JJ.Chronic,low-level exposure to diisopropylflu- rophosphate causes protracted impairment of spatial navigation learning.Psychopharmacology (Berl),1997,129:183-191.
[70]Schmuck G,Mihail F.Effects of the carbamates fenoxycarb,propamocarb and propoxur on energy supply,glucose utilization and SH-groups in neurons.Arch Toxicol,2004,78:330-337.
[71]Guillette EA,Meza MM,Aquilar MG,et al.An anthropological approach to the evaluation of preschool children exposed to pesticides in Mexico.Environ.Health Perspect,1998,106:347-353.
[72]Rohlman DS,Arcury TA,Quandt SA,et al.Neurobehavioral performance in preschool children from agricultural and non-agricultural communities in Oregon and North Carolina.Neurotoxicology,2005,26:589-98.
[73]Grandjean P,Harari R,Barr DB,et al.Pesticide exposure and stunting as independent predictors of neurobehavioral deficits in Ecuadorian school children.Pediatrics,2006,117:546-56.
[74]Ruckart PZ,Kakolewski K,Bove FJ,et al.Long-term neurobehavioral health effects of methyl parathion exposure in children in Mississippi and Ohio.Environ Health Perspect,2004,112:46-51.
[75]Patricia Sanchez Lizardi,Mary Kay O'Rourke,Richard J.Morris.The Effects of Organophosphate Pesticide Exposure on Hispanic Children's Cognitive and Behavioral Functioning.J Pediatr Psychol,2008,33:91-101.
[76]Young JG,Eskenazi B,Gladstone EA,et al.Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates.Neurotoxicology.2005,26:199-209.
[77]Whyatt RM,Rauh V,Barr DB,et al.Prenatal insecticide exposures and birth weight and length among an urban minority cohort.Environ Health Perspect,2004,112:1125-1132.
[78]U.S.Environmental Protection Agency.Administrator's Announcement.http://www.epa.gov/ pesticides/announcement 6800.htm,accessed 11 October 2000.
[79]Kurtz J.Dissociated behavioural and cholinesterase decrements following malathion exposure.Toxicol Appl Pharmacol,1977,42:589-594.
[80]Levin ED,Addy N,Nakajima A,et al.Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats.Dev Brain Res.2001,130:83-89.
[81]Crowder LA,Lanzaro GC,Whitson RS.Behavioral effects of methyl parathion and toxaphene exposure in rats.J Environ Sci Health B,1980,15:365-378.
[82]Aldridge JE,Levin ED,Seidler FJ,et al.Developmental Exposure of Rats to Chlorpyrifos Leads to Behavioral Alterations in Adulthood,Involving Serotonergic Mechanisms and Resembling Animal Models of Depression.Environ Health Perspect,2005,113:527-531.
[83]Stamper CR,Balduini W,Murphy SD,et al.Behavioral and biochemical effects of postnatal parathion exposure in the rat.Neurotoxicol Teratol,1988,10:261-266.
[84]Icenogle LM,Christopher NC,Blackwelder WP,et al.Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation.Neuroioxicol Teratol,2004,26:95-101.
[85]Roy TS,Seidler FJ,Slotkin TA:Morphologic effects of subtoxic neonatal chlorpyrifos exposure in developing rat brain:regionally selective alterations in neurons and glia.Brain Res Dev Brain Res,2004,148:197-206.
[86]Santos HR,Cintra WM,Aracava Y.Pine density and dendritic branching pattern of hippocampal CA1 pyramidal neurons in neonatal rats chronically exposed to the organophosphate paraoxon.Albuquerque Neurotoxicology,2004,25:481-494.
[87]Lassiter T,Brone S.Gestational exposure to chlopyrifos:qualitative and quantitative neuropathological changes in the fetal neocortex.Toxicologist,2002,66:632-53.
[88]Qiao D,Seidier FJ,Abreu-Villaca Y,et al.Chlorpyrifos exposure during neurulation:cholinergic synaptic,dysfunction and cellular alterations in brain regions at adolescence and adulthood.Dev Brain Res.2004,148:43-52.
[89]Dam K,Seidier FJ.Slotkin TA,et al.Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity.Brain Res Dev Brain Res,2000,121:179-187.
[90]Rice D,Barone S,Jr.Critical periods of vulnerability for the developing nervous system:evidence from humans and animal models.Environ.Health Perspect,2000,108:511-533.
[91]HunterDL,LassiterTL,Padilla S.Gestational exposure to chlorpyrifos:comparative distribution of trichloropyridinol in the fetus and dam.Toxicol Appl Pharmacol,1999,158:16-23.
[92]Pope CN,Chakraborti TK,Chapman ML,et al.Comparison of in vivo cholinesterase inhibition in neonatal and adult rats by three organophosphorothioate insecticides.Toxicology,1991,68:51-61.
[93]Chanda SM,Harp P,Liu J.et al.Comparative developmental and maternal neurotoxicity following acute gestational exposure to chlorpyrifos in rats.J Toxicol Environ Health,1995,44:189-202.
[94]Chanda SM,Pope CN.Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats.Pharmacol Biochem Behav,1996,53:771-776.
[95]Lassiter TL,Padilla S,Mortensen SR,et al.Gestational exposure to chlorpyrifos:apparent protection of the fetus? Toxicol Appl Pharmacol.1998,152:56-65.
[96]Atterberry TT,Burnett WT,Chambers JE.Age-related differences in parathion and chlorpyrifos toxicity in male rats:target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism.Toxicol.Appl.Pharmacol,1997,147:411-418.
[97]Slotkin TA.Cholinergic systems in brain development and disruption by neurotoxicants:nicotine,environmental tobacco smoke,organophosphates.Toxicol Appl Pharmacol,2004,198(2):132-151.
[98]Whitney KD,Seidier FJ,Slotkin TA.Developmental neurotoxicity of chlorpyrifos:cellular mechanisms.Toxicol Appl Pharmacol,1995,134:53-62.
[99]Qiao D,Seidier FJ,Slotkin TA.Developmental neurotoxicity of chlorpyrifos modeled in vitro:comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC 12 and C6 cells.Environ Health Perspect,2001,109:909-913.
[100]Zheng T,Zahm SH,Cantor KP,Weisenburger DD,Zhang Y,Blair A.Agricultural exposure to carbamate pesticides and risk of non-Hodgkin lymphoma.J Occup Environ Med,2001,43(7):641-649.
[101]Blair A,Zahm SH.Agricultural exposures and cancer.Environ Health Perspect,1995,103:205-208.
[102]Gurney JG,Smith MA,Olshan AF,et al.Clues to the etiology of childhood brain cancer:N-nitroso compounds,polyomaviruses,and other factors of interest.Cancer Invest,2001,19:630-640.
[103]Efird JT,Holly EA,Preston-Martin S,et al.Farm-related exposures and childhood brain tumours in seven countries:results from the SEARCH International Brain Tumour Study.Paediatr Perinat Epidemiol,2003,17:201-211.
[104]Daniels JL,Olshan A F,Savitz DA.Pesticides and childhood cancers.Environ Health Perspect,1997,105:1068-1077.
[105]世界资源研究所,联合国环境规划署,联合国开发计划署等编.世界资源报告—环境变化与人体健康(1998-1999).北京:中国环境科学出版社,1999.3.
[106]Colborn T.Endocrine disruption from environmental toxicant.In:Rom WN,ed.Environmental and Occupational Medicine,3rd ed.Philadelphia:Lippincott-Raven Publishers,1998.
[107]Andrea CG.Environmental toxicant effects on neuroendocrine function.Endocrine,2001,14:235-246.
[108]Padungtod C,Lasley BL,Christiani DC,et al.Reproductive hormone profile along pesticide factory workers.J Occup Env Med,1998,40:1038-1047.
[109]詹宁育,王心如,王沭沂,等.辛硫磷育氰戊菊酯对大鼠睾丸的联合毒性作用.中华劳动卫生职业病杂志.2001,19(4):261-264.
[110]王捷,朱宏宇,胡翠清.农药生殖毒性的回顾.农药,2005,44(11):489-505.
[111]刘学,李贤相,江隆久,等.U-Cell法测定农药对男性精子机能影响的分析.疾病控制与防治杂志,1999,3(2):84-87.
[112]Recio R,Robbins WA,Borja-Aburto V,et al.Organophosphorous pesticide exposure increases the frequency of sperm sex null aneuploidy.Environ Health Perspect,2001,109:1237-1040.
[113]Padungtod C,Lasley BL,Christiani DC,et al.Reproductive hormone profile among pesticide factory workers.J Occup Environ Med,1998,40:1038-1047
[114]张霜红,王锦珍,王治明.职业性农药接触对女工生殖功能的影响.现代预防医学,2004,31(5):664-665.
[115]Chia SE,Shi LM.Review of recent epidemiological studies on patemal occupations and birth defects.Occupational and Environmental Medicine,2002,59(3):149-155.
[116]罗永有.我国出生缺陷干预现状与发展趋势.实用预防医学,2005,12(2):458-461.
[117]刘守庆,石宝增.临沂市某农药厂环境染染与新生儿出生缺陷的流行病学调查研究.预防医学文献信息,2002,8(3):273-274.
[118]Shaw GM,Wasserman CR,O'Malley CD,et al.Maternal pesticide exposure from multiple sources and selected congenital anomalies.Epidemiology,1999,10:60-62.
[119]Karanth S.OLiver K,Liu J,et al.In vivo interaction between chlorpyrifos and parathion in adult rats:sequence of administration can markedly influence toxic outcome.TOxicol Appl Pharmacol,2001,177:247-255.
[120]何凤生,陈署旸.混配农药中毒的防治研究.中华医学信息导报,2002,11:16-17.
[121]欧阳明,林雪梅,盛书样,等.评价杀虫剂混用联合作用的六种方法比较.农药科学与管理,1997,18(1):20-29.
[122]Large P,Wiezorek WD.The effects of diethyldithiocarbamate on the acute toxicity and the acetylcholinesterase inhihition by methylparathion in mice.Acta Biol Med Germ,1975,34(2):427-433.
[123]Hayes WJ,Laws ER.Handbook of pesticide toxicology.New York:San Francisco Academic Ptess,1991,2:588
[124]Mansour NA,Eldefrawi ME,Toppodaza A,et al.Toxicological studies on the Egyptian cotton leafworm,prodenia litura.Ⅵ.potentiation and antagonism of organophosphorus and carbamate insecticides.J Eco Entomol.1966,59(2):307-311.
[125]Petroianu GA,Nurulain SM,Ararat K,et al.Effect of pyridostigmine,pralidoxime and their combination on sarvival and cholinesterase activity in rats exposed to the organophosphate paraoxon.Arch Toxicol.2006,80(11):777-784.
[126]Eckert S,Eyer P,Mückter H,et al.Kinetic analysis of the protection afforded by reversible inhibitors against irreversible inhibition of acetylcholinesterase by highly toxic organophosphorus compounds.Biochem Pharmacol,2006,72(3):344-357.
[127]Keplinger ML,Deichmann WB.Acute toxicity of combinations of pesticides.Toxicol Appl Pharmacol,1967,10(3):586-598.
[128]Sultatos LG,Murphy SD.Kinetic analysis of the microsomal biotransmation of the phosphorothioate insecticides chlorpyrifos and parathion.Fundan Appl Toxicol,1983,3(1):16-21
[129]孙金秀,陈波,姚佩佩.农药混剂联合毒性评价.卫生研究,2000,29(2):65-68.
[130]颜冬云,蒋新,余贵芬,等.有机磷农药对乙酰胆碱酯酶活性的联合抑制作用.农药,2006,45(1):31-34.
[1]Wesseling C,Keifer M.Ahlborn A,McConeel R,Moon J,Risenstock L,et al.Long-term neurobehavioral effects of mild poisoning with organophosphate and N-methyl carbamate pesticides among banana workers.Int J Occup Health,2002,8:27-34.
[2]Jamal GA.Neurological syndromes of organophosphorus compounds.Adverse Drug React Toxicol Rev,1997,16:133-170.
[3]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Arch Environ Health,2003,58:484-497.
[4]Ahmed GM and Davies DR.Chronic organophosphate exposure:towards the definition of a neuropsychiatric syndrome.J Nutr Environ Med,1997,7:169-176.
[5]Colosio C,Tiramani M,Maroni M.Neurobehavioral effects of pesticides:state of the art.Neurotoxicology,2003,24:577-591.
[6]Gershon S and Shaw FB.Psychiatric sequelae of chronic exposure to organophosphate insecticides.Lancet,1961,1:1371-1374.
[7]Metcalf DR,Holmes JH.EEG,Psychological and neurological alterations in human with organophosphorus exposure.Ann NY Acad Sci,1969,160:357-365
[8]Savage EP,Keefe TJ,Mounce LM.Heaton RK,Lewis JA,Burcar PJ.Chronic neurological sequelae of acute organophosphate pesticide poisoning.Arch Environ Health,1988.43:38-45.
[9]Rosenstock L,Keifer M,Daniell W,McConnell R,Claypoole K.Chronic central nervous system effects of acute organophosphate pesticide intoxication.Lancet,1991,338:223-227.
[10]Jamal GA and Julu P.Low level exposures to organophosphorus esters may cause neurotoxicity.Toxicology,2002,181:23-33.
[11]Kamel F and Hoppin JA.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[12]Stephens R,Spurgeon A,Calvert IA,Beach J,Levy LS,Berry H,et al.Neuropsychological effects of long-term exposure to organophosphates in sheep dippers.Lancet,1995,345:1135-1139
[13]Bazylewicz-Walczak B,Majczakowa W,Szymczak M.Behavioral effects of occupational exposure to organophosphorous pesticides in female greenhouse planting workers.Neurotoxicology,1999,20:819-826.
[14]Prendergast MA,Terry AV,Buccafusco JJ.Effects of chronic,low-level organophosphate exposure on delayed recall,discrimination,and spatial learning in monkeys and rats.Neurotoxicol Teratol,1998,20:115-122.
[15]Kassa J,Koupilova M,Vachek J.The influence of low-level sarin inhalation exposure on spatial memory in rats.Pharmacol Biochem Behav,2001,70:175-179.
[16]Canadas F,Cardona D,D(?)vila E,Sanchez-Santed F.Long-term neurotoxicity of chlorpyrifos:spatial learning impairment on repeated acquisition in a water maze.Toxicol Sci,2005,85:944-951.
[17]Sanchez-Santed F,Ca(?)adas F,Flores P,L(?)pez-Grancha M,Cardona D.Long-term functional neurotoxicity of paraoxon and chlorpyrifos:behavioural and pharmacological evidence.Neurotoxicol Teratol,2004,26:305-317.
[18]Duffy FH and Burchfield JL.Long term effects of the organophosphate sarin on EEGs in monkeys and humans.Neurotoxicology,1980,1:667-689.
[19]Song X,Seidler FJ,Saleh JL,Zhang J,Padilla S,Slotkin TA.Cellular mechanisms for developmental toxicity of chlorpyrifos:targeting the adenylyl cyclase signaling cascade.Toxicol Appl Pharmaco,1997,145:158-174.
[20]Prendergast MA,Terry AV,Buccafusco JJ.Chronic,low-level exposure to diisopropylfluorophosphate causes protracted impairment of spatial navigation learning.Psychopharmacology (Berl),1997.129:183-91.
[21]Schmuck G and Mihail F.Effects of the carbamates fenoxycarb,propamocarb and propoxur on energy supply,glucose utilization and SH-groups in neurons.Arch Toxicol,2004,78:330-337.
[22]Terry AV,Stone JD,Buccafusco JJ,Sickles DW,Sood A,Prendergast MA.Repeated exposures to subthreshold doses of chlorpyrifos in rats:hippocampal damage,impaired axonal transport,and deficits in spatial learning.J Pharmacol Exp Ther,2003,305:375-384.
[23]Goekoop R,Scheltens P,Barkhof F,Rombouts S.Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation—a pharmacological fMRI study.Brain,2006,129:141-157.
[24]Eichenbaum H.Hippocampus cognitive processes and neural representations that underlie declarative memory.Neuron,2004,44:109-120.
[25]Gron G,Brandenburg I,Wunderlich AP,Riepe MW.Inhibition of hippocampal function in mild cognitive impairment:targeting the cholinergic hypothesis.Neurobio Aging,2006,27:78-87.
[26]Zhang M,Wang A,He W,et al.Effects of fluoride on the expression of NCAM,oxidative stress,and apoptosis in primary cultured hippocampal neurons.Toxicology,2007,236:208-216.
[27]Harkins J,Arsenault M,Schlesinger K,et al.Induction of neuronal functions:acetylcholine-induced acetylcholinesterase activity in mouse neuroblastoma cells.Proc Nat Acad Sci USA,1972,69 (11):3161-3164.
[28]Mosmann T.Rapid colorimetric assay for cellular growth and survival:application to proliferation and neurotoxicity assays.J Immunol Methods,1983,65:55-63.
[29]Schengrund C and Marangos P.Neuron-specific enolase levels in primary cultures of neurons.J Neurosci,2004,5:305-311.
[30]Wang W,Iyo A,Miguel-Hidalgoa J,Regunathana S,Zhu M.Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons.Brain Res,2006,1084:210-216.
[31]Rosenblum K,Futter M,Jones M,Hulme EC,Bliss TV.ERK1/2 regulation by the muscarinic acetylcholine receptors in neurons.J Neurosci,2000,20:977-985.
[32]Yan GM,Lin SZ,Irwin RP,Paul SM.Activation of muscarinic cholinergic receptors blocks apoptosis of cultured cerebellar granule neurons.Mol Pharmacol,1995,47:248-257.
[33]Caughlan C,Newhous K,Namgung UK,Xia Z.Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases.Toxicol Sci,2004,78:125-134.
[34]Robinson MJ and Cobb MH.Mitogen-activated protein kinase pathways.Curr Opin Cell Biol,1997,9:180-186.
[35]Atkins CM,Selcher JC,Petraitis JJ.trzaskos JM,Sweatt JD.The MAPK cascade is required for mammalian associative learning.Nature Neurosci,1998,1:602-609.
[36]Xia Z,Dickens M,Raingeaud J,Davis RJ,Greenberg ME.Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.Science,1995,270:1326-1331
[37]Hetman M,Kanning K,Cavanaugh JE,Xia Z.Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol-3 kinase.J Biol Chem,1999,274:22569-22580.
[38]Singer CA,Figueroa-Masot XA,Batchelor RH,Dorsa DM.The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons.J Neurosci,1999,19:2455-63.
[39]Szatmari E,Katarzyna B,Kalita,Kharebava G,Hetman M.Role of kinase suppressor of ras-1 in neuronal survival signaling by extracellular signal-regulated kinase 1/2.J Neurosci,2007,27:11389-11400.
[40]Araki W and Wurtman RJ.Increased expression of amyloid precursor protein and amyloid precursor-like protein 2 during trophic factor withdrawal-induced death of neuronal PC 12 cells.Mol Brain Res,1998,56:169-177.
[41]Murray B,Alessandrini A.Cole A,Yee A,Furshpan E.Inhibition of the ERKl/2 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity.Proc Natl Acad Sci USA,1998,95:11975-11980.
[42]Alessandrini A,Namura S,Moskowitz MA,Bonventre JV.MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia.Proc Natl Acad Sci USA,1999,96:12866-12869.
[43]Stanciu M,Wang Y,Kentor R,Burke N,Watkins S,Kress G,et al.Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures.J Biol Chem,2000,275:12200-12206.
[44]Fukunaga K and Miyamoto E,1998,Mol Neurobiol 16:79-95.
[45]Takagi N,Miyake-Takagi K,Takagi K,Tamura H,Takeo S.Altered extracellular signal-regulated kinase signal transduction by the muscarinic acetylcholine and metabotropic glutamate receptors after cerebral ischemia.J Biol Chem,2002.277:6382-6390.
[46]Thoenen H.Neurotrophins and neuronal plasticity.Science,1995,270:593-598.
[47]Bowden CA,Krenzelok EP.Clinical applications of commonly used contemporary antidotes.A US perspective.Drug Saf,1997.16:9-47.
[48]Alessi DA,Cuenda A,Cohen P,Dudley DT,Saltiel AR.PD98059 is a specific inhibitor of the activation of mitogen activated protein kinase in vitro and in vivo.J Biol Chem,1995,270:27489-27494.
[49]Jameson RR,Seidler FJ,Slotkin TA.Nonenzymatic functions of acetylcholinesterase splice variants in the developmental neurotoxicity of organophosphates:chlorpyrifos,chlorpyrifos oxon,and diazinon.Environ Health Perspect,2007,115:65-70.
[50]Das KP and Barone S Jr.Neuronal differentiation in PC 12 cells is inhibited by chlorpyrifos and its metabolites:Is acetylcholinesterase inhibition the site of action? Toxicol Appl Pharmacol.1999,160:217-230.
[51]Kaneko N,Okano H,Sawamoto K.Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb.Genes Cells,2006,11: 1145-1159.
[52]Yan GM,Lin SZ,Irwin RP,Paul SM.Activation of muscarinic cholinergic receptors blocks apoptosis of cultured cerebellar granule neurons.Mol Pharmacol,1995,47:248-257.
[53]White J.Pleasure into pain:the consequences of long-term opioid use.Addict Behav,2004,29:1311-1324.
[54]Hochberg Z,Pacak K,Chrousos G.Endocrine withdrawal syndromes.Endocr Rev,2003,24:523-538.
[55]Russell RW,Overstreet DH,Cotman CW,Carson VG,Churchill L,Dalglish FW,et al.Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase,diisopropyl fluorophosphate.J Pharmacol Exp Ther,1975,192:73-85.
[56]Schwab BW,Costa LG,Murphy SD.Muscarinic receptor alterations as a mechanism of anticholinesterase tolerance.Toxicol Appl Pharmacol,1983,71:14-23.
[57]Costa LG and Murphy SD.Unidirectional cross-tolerance between the carbamate insecticide Propoxur and the organophosphate Disulfoton in mice.Fundam Appl Toxicol,1983,3:483-488.
[58]Bushnell PJ,Kelly KL,Ward TR.Repeated inhibition of cholinesterase by chlorpyrifos in rats:behavioral,neurochemical and pharmacological indices of tolerance.J Pharmacol Exp Ther,1994,270:15-25.
[59]Slotkin TA,Cousins MM,Tate CA,Seidier FJ.Persistent cholinergic presynaptic deficits after neonatal chlorpyifos exposure.Brain Res,2001,902:229-243.
[60]Kaufer D,Friedman A,Seidman S,Soreq H.Anticholinesterases induce multigenic transcriptional feedback response suppressing cholinergic neurotransmission.Chem Biol Interact,1999,119:349-60.
[61]Liu J and Pope CN.Effects of chlorpyrifos on high-affinity choline uptake,and [~3H]hemicholinium-3 binding in rat brain.Fundam Appl Toxicol,1996,34:84-90.
[62]Plotkin DA and Jarvik LF.Cholinergic dysfunction in Alzheimer's disease:cause or effect? Prog Brain Res,1986,65:91-102.
[63]Schliebs R and Arendt T.The significance of the cholinergic system in the brain during aging and in Alzheimer's disease.J Neural Transm,2006,113:1625-1644.
[1]Hochberg Z,Pacak K.Chrousos G.Endocrine withdrawal syndromes.Endocr Rev,2003,24:523-538.
[2]White J.Pleasure into pain:the consequences of long-term opioid use.Addict Behav,2004,29:1311-1324.
[3]Zhang M,Wang A,He W,He P,Xu B,Xia T,et al.2007.Effects of fluoride on the expression of NCAM,oxidative stress,and apoptosis in primary cultured hippocampal neurons.Toxicology,236:208-216.
[4]Kamel F and Hoppin JA.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[5]Rosenstock L,Keifer M,Daniell W,McConnell R,Claypoole K.Chronic central nervous system effects of acute organophosphate pesticide intoxication.Lancet,1991,338:223-227.
[6]Barnes SM and Denz FA.The Reduction of Rats to Diets Containing Octamethyl Pyrophosphoramide (Schraden) and O,O-diethyl-5-ethylmercaptethanolthio-phospha(tesy stox) Br.J.Industr.Med.,1954,11:11-19.
[7]Rider JA,Eillineood LW,and Coon JM.Production of Tolerance in th e Rat to Octamethyl (OMPA),Proc Soc Exp Biol Med.1952,81:4 55-459.
[8]Nobuhiro Konno,Toru Yamauchi,Yasuaki Yamaguchi and Masaaki Fukushima.Protective effect of pretreatment against the acute toxicity of formulated cyanofenphos in hens.The Tohoku Journal of Experimental Medicine.1984,142(2):155-163.
[9]Bushnell PJ,Kelly KL,Ward TR.Repeated inhibition of cholinesterase by chlorpyrifos in rats:behavioral,neurochemical and pharmacological indices of tolerance.J Pharmacol Exp Ther.1994,270(1):15-25.
[10]Bushnell PJ,Padilla SS,Ward T,Pope CN,Olszyk VB.Behavioral and neurochemical changes in rats dosed repeatedly with diisopropylfluorophosphate.J Pharmacol Exp Ther.1991,256(2):741-50
[11]Bushnell PJ,Pope CN,Padilla S.Behavioral and neurochemical effects of acute chlorpyrifos in rats:tolerance to prolonged inhibition of cholinesterase.The Journal of pharmacology and experimental therapeutics.1993,266(2):1007-1017.
[12]Kornnika Khanobdee,Naiphinich Kotchabhakdi,Piyarat Govitrapong.Development of tolerance to monocrotophos.Thammasat Int J Sc.Tech.1999,4(1):61-67.
[13]Jeffrey Cohn and Robert C.Macphail.Chlorpyrifos produces selective learning deficits in rats working under a schedule of repeated acquisition and performance.J Pharmacol Exp Ther.1997,283(1):312-320.
[14]Luczak C,Gralewicz S,Górny R.Tblerance to chlorphenvinphos in rats assessed on the basis of changes in locomotor behavior in rotating wheels.Pol J Occup Med Environ Health.1992,5(1):43-54
[15]孙运光.有机磷农药所致耐受性的研究进展.国外医学卫生学分册,2001,28(6):325-329.
[16]Schwab BW,Costa LG,Murphy SD.Muscarinic receptor alterations as a mechanism of anticholinesterase tolerance.Toxicol Appl Pharmacol,1983,71:14-23.
[17]Fitzgerald BB,Costa LG.Medulation of M_1 and M_2 muscarinic receptor subtypesfollowing repeated organophosphate exposure in rats.Toxicol Appl Pharmacol,1992,117:122-125.
[18]孙运光,周志俊,胡云平.乐果亚急性染毒诱导大鼠耐受以及对大鼠脑组织M受体的影响,环境与职业医学,2003,20(3):154-158.
[19]伍一军,孙健英,鲍凯瑞.有机磷类杀虫剂对脑突触体烟碱型自主受体功能的影响.中华劳动卫生职业病杂志,2003,21(3):188-190.
[20]Gazit H,Silman I,and Dudai Y.Administration of an organophosphate causesa decrease in muscarinic receptor levels in rat brain.Brain Res.1979,174:315-356.
[21]Slotkin TA,Cousins MM,Tate CA,Seidler FJ.Persistent cholinergic presynaptic deficits after neonatal chlorpyifos exposure.Brain Res 2001,902(2):229-243.
[22]Jing Liu Carey N.Pope.Comparative presynaptic neurochemical changes in rat striatum following exposure to chlorpyrifos or parathion.J Toxicol Environ Health.1998,53(7):531-544.
[23]Ward TR,Mundy WR.Organophosphorus compounds preferentially affect second messenger systems conpled to M_2/M_4 receptors in rat frontal cortex.Brain Res Bull,1996,39:49-55.
[24]Russell RW,Overstreet DH,Cotrnan CW,Carson VG,Churchill L,Dalglish FW,VaLsquez BJ.Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase,diisopropylfluorophosphate.J Pharmacol Exp Ther,1975,192:73-85.
[1]杨霓云,刘征涛,王宏,等.五氯苯酚与邻氯苯酚和2,4-二氯苯酚对斑马鱼的联合毒性[J].环境科学研究,2006,19(6):145-148.
[2]杨永滨,刘征涛,郑明辉,等.卤代酚对斑马鱼的急性联合毒性效应研究.环境科学研究.2007,20(2):5-8.
[3]Boon P E,Van der Voet H,Van Raaij M T,et al.Cumulative risk assessment of the exposure to organophosphorus and carbamate insecticides in the Dutch diet.Food Chem Toxicol,2008,46:3090-3098.
[4]Rice P J,Rice P J,Arthur E L,et al.Advances in pesticide environmental fate and exposure assessments.J Agric Food Chem,2007,55(14):5367-5376.
[5]Boobis AR,Ossendorp BC,Banasiak U,et al.Cumulative risk assessment of pesticide residues in food.Toxicol Lett.2008,180(2):137-150.
[6]Jensen AF,Petersen A,Granby K,et al.Cumulative risk assessment of the intake of organophosphorus and carbamate pesticides in the Danish diet.Food Addit Contam.2003,20(8):776-785.
[7]文一,潘家荣.有机磷农药的联合毒性研究进展.环境与健康杂志,2007,24(7):553-555.
[8]孙金秀,陈波,姚佩佩.农药混剂联合毒性评价.卫生研究,2000,29(2):65-66.
[9]孔祥锋,陈婉蓉,倪兵,等.H_2O_2对大鼠神经细胞的氧化损伤及硒的保护作用.卫生毒理学杂志,2000,14(2):91-94.
[10]祁爱群,邱俭,肖林,等.糖皮质激素对原代培养的海马细胞中p44/42的快速非基因组激活作用.自然科学进展,2004,14(7):760-766.
[11]Caughlan A,Newhous K,Namgung U K,et al.Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases.Toxicol Sci,2004,78(1):125-134.
[12]Kamel F,Hoppin,J A.Association of pesticide exposure with neurologic dysfunction and disease.Environ Health Perspect,2004,112:950-958.
[13]Petroianu G A,Nurulain S M,Arafat K,et al.Effect of pyridostigmine,pralidoxime and their combination on survival and cholinesterase activity in rats exposed to the organophosphate paraoxon.Arch Toxicol,2006,80(11):777-784.
[14]Golomb B A.Acetylcholinesterase inhibitors and Gulf War illnesses.Proc Natl Acad Sci USA,2008,105(11):4295-4300.
[15]Rosenblum K,Futter M,Jones M,et al.ERK1/2 regulation by the muscarinic acetylcholine receptors in neurons.J Neurosci,2000,20(3):977-985.
[16]Robinson M J and Cobb M H.Mitogen-activated protein kinase pathways.Curr Opin Cell Biol,1997,9:180-186.
[1]Nguyena TD,Maquartb FX,Monboisse JC.Ionizing radiations and collagen metabolism:from oxygen free radicals to radio-induced late fibrosis.Radia Physics and Chem,2005,72:381-386.
[2]Leonard SS,Harris GK,Shi X.Metal-induced oxidative stress and signal transduction.Free Rad Biol Med,2004,37:1921-1942.
[3]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Arch Environ Health,2003,58:484-497.
[4]Milatovic D,Gupta RC,Aschner M.Anticholinesterase toxicity and oxidative stress.Sci World J,2006,6:295-310.
[5]Dettbarn WD.Milatovic D.and Gupta RC.Oxidative stress in anticholinesterase-induced excitotoxicity.In:R.C.Gupta,Editor,Toxicology of Organophosphate and Carbamate Compounds,Academic Press/Elsevier,Amsterdam,2006,511-532.
[6]Esterbauer H,Cheeseman KH.Determination of aldehydic lipid peroxidation products:malonaldehyde and 4-hydroxynonenal.Methods Enzymol,1990,186:407-421.
[7]Spitz DR,Oberley LW.An assay for superoxide dismutase activity in mammalian tissue homogenates.Anal Biochem,1989,179:8-18.
[8]El-Missiry MA,Abou-Seif M.Photosensitization induced reactive oxygen species and oxidative damage in human erythrocytes.Cancer Lett,2000,158:155-163.
[9]Paglia DE,Valentine WN.Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.J Lab Clin Med,1967,70:158-170.
[10]Gupta RC,Milatovic S,Dettbarn WD,Aschner M,Milatovic D.Neuronal oxidative injury and dendritic damage induced by carbofuran:protection by memantine.Toxicol Appl Pharmacol,2007,219:97-105.
[11]Kamboj SS,Kumar V,Kamboj A,Sandhir R.Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran exposure.Cell Mol Neurobiol,2008,28:961-969.
[12]Rai DK,Sharma B.Carbofuran-induced oxidative stress in mammalian brain.Mol Biotechnol,2007,37:66-71.
[13]Kamboj A,Kiran R,Sandhir R.Carbofuran-induced neurochemical and neurobehavioral alterations in rats:attenuation by N-acetylcysteine.Exp Brain Res,2006,170:567-575.
[14]Shadnia S,Azizi E,Hosseini R,Khoei S,Fouladdel S,Pajoumand A,et al.Evaluation of oxidative stress and genotoxicity in organophosphorus insecticide formulators.Hum Exp Toxicol,2005,24(9): 439-445.
[15]Ranjbar A,Pasalar P,Abdollahi M.Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers.Hum Exp Toxicol,2002,21(4):179-182.
[16]Tuzmen N,Candan N,Kaya E,Demiryas N.Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver.Cell Biochem Funct,2008,26(1):119-124.
[17]Yu F,Wang Z,Ju B,Wang Y,Wang J,Bai D.Apoptotic effect of organophosphorus insecticide chlorpyrifos on mouse retina in vivo via oxidative stress and protection of combination of vitamins C and E.Exp Toxicol Pathol,2008,59(6):415-423.
[18]Slotkin TA,Oliver CA,Seidler FJ.Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline,alone or in combination.Brain Res Dev Brain Res,2005,157(2):172-180.
[19]Crumpton TL,Seidler FJ,Slotkin TA.Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos? Dev Brain Res.2000,121:189-195.
[20]Qiao D,Seidler FJ,Slotkin TA.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicol Appl Pharmacol,2005,206:17-26.
[21]Saulsbury MD,Heyliger SO,Wang K,Johnson DJ.Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells.Toxicology,2009.
[22]Giordano,G.,Afsharinejad,Z.,Guizzetti,M.,Vitalone,A.,Kavanagh,T.J.and Costa,L.G.Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency.Toxicol Appl Pharmacol,2007,219:181-189.
[23]Danielisova V,Nemethova M,Gottlieb M and Burdal J.Changes of endogenous antioxidant enzymes during ischemic tolerance acquisition.Neurochem Res,2005,30:559-565.
[24]Borrego A,Zamora ZB,Gonza'lez R,et al.Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats.Mediators Inflamm,2004,13:13-19.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |