The relationship between diphenylamine structure and NSAIDs-induced hepatocytes injury

doi:10.1016/j.toxlet.2009.01.005

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	The relationship between diphenylamine structure and NSAIDs-induced hepatocytes injury
	Li, Yan 1,2; Qi, Xin-ming2 ; Xue, Xiang 1,2; Wu, Xiong-fei 1,2; Wu, Yuan-feng 1,2; Chen, Min 1,2; Xing, Guo-zhen 1,2; Luan, Yang 2; Ren, Jin2
刊名	TOXICOLOGY LETTERS
	2009-04-25
卷号	186 期号:2 页码:111-114
关键词	Mitochondria Liver injury NSAIDs Diphenylamine structure
ISSN号	0378-4274
DOI	10.1016/j.toxlet.2009.01.005
文献子类	Article
英文摘要	Objective: Many nonsteroidal anti-inflammatory drugs (NSAIDs) with diphenylamine structure induce severe hepatotoxicities. We evaluated the role of diphenylamine structure in liver injuries induced by these NSAIDs. Methods: Effects of diphenylamine, diclofenac and tolfenamic acid on mitochondrial permeability transition (MPT) and efflux of calcium in isolated liver mitochondria as well as on cellular ATP content and mitochondrial membrane depolarization in rat primary hepatocyte cultures were examined. Results: Diclofenac and tolfenamic acid induced cyclosporine A (CsA)-sensitive mitochondrial swelling and membrane depolarization in isolated liver mitochondria. Only diclofenac caused the release of calcium in isolated liver mitochondria. Diphenylamine had no effects on isolated liver mitochondria. All three compounds decreased ATP content and induced mitochondrial membrane depolarization. CsA attenuated these effects, suggesting MPT might be involved in the hepatotoxicities caused by diphenylamine, diclofenac and tolfenamic acid. SKF-525A, a general inhibitor of CYP450, markedly inhibited the injury induced by diphenylamine, but not diclofenac or tolfenamic acid. Conclusion: The hepatotoxicities caused by diclofenac and tolfenamic acid may be attributed to the mitochondrial dysfunction induced by these drugs instead of the diphenylamine structure per se. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
资助项目	National Key Technologies RD Program[2008ZX09305-007]
WOS关键词	NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; ISOLATED RAT HEPATOCYTES ; HEPATOTOXICITY ; CELLS ; LIVER
WOS研究方向	Toxicology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000264976400006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279261]
专题	药物安全性评价中心中科院受体结构与功能重点实验室信息中心新药研究国家重点实验室药理学第一研究室
通讯作者	Ren, Jin
作者单位	1.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Li, Yan,Qi, Xin-ming,Xue, Xiang,et al. The relationship between diphenylamine structure and NSAIDs-induced hepatocytes injury[J]. TOXICOLOGY LETTERS,2009,186(2):111-114.
APA	Li, Yan.,Qi, Xin-ming.,Xue, Xiang.,Wu, Xiong-fei.,Wu, Yuan-feng.,...&Ren, Jin.(2009).The relationship between diphenylamine structure and NSAIDs-induced hepatocytes injury.TOXICOLOGY LETTERS,186(2),111-114.
MLA	Li, Yan,et al."The relationship between diphenylamine structure and NSAIDs-induced hepatocytes injury".TOXICOLOGY LETTERS 186.2(2009):111-114.