Pharmacometabonomic Phenotyping Reveals Different Responses to Xenobiotic Intervention in Rats

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• 作者：Houkai Li ; Yan Ni ; Mingming Su ; Yunping Qiu ; Mingmei Zhou ; Mingfeng Qiu ; Aihua Zhao ; Liping Zhao ; Wei Jia
• 刊名：Journal of Proteome Research
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：6
• 期：4
• 页码：1364 - 1370
• 全文大小：338K
• 年卷期：v.6,no.4(April 2007)
• ISSN：1535-3907

文摘

In conventional pharmacological studies, intersubject differences within an animal strain are normallyneglected, leading to variations in pharmacological outcomes in response to the same stimulus. Usingtwo classical experimental models, the Streptozotocin (STZ)-induced diabetic model of Wistar rats andthe high-energy, diet-induced obesity model of Sprague-Dawley rats, we demonstrate that the differentoutcomes of STZ or diet intervention are closely associated with variation in predose (baseline) urinarymetabolic profiles of the rats. The pharmacometabonomic analysis of predose metabolic profilesindicates that the intersubject difference is, to a great extent, associated with gut-microbiota, whichpredisposes different pathophysiological outcomes upon diet alteration or chemical stimulus. Wehypothesize that there may exist an important association between observations from these two modelsand the obese/diabetic human population in that subtle variations in metabolic phenotype maypredetermine different systems' responses to xenobiotic perturbation, ultimately leading to variedpathophysiological processes. Results from two independent models also suggest that the pharmacometabonomics approach is of great importance in the study of pharmacology and clinical drugevaluations, where endogenous metabolite signatures of predose individuals should be taken intoconsideration to minimize intersubject difference and the resulting variation in the postdose pharmacological outcomes.