The relationship between diphenylamine structure and NSAIDs-induced hepatocytes injury
文献类型：期刊论文
| 作者 | Li, Yan1,2; Qi, Xin-ming2 ; Xue, Xiang1,2; Wu, Xiong-fei1,2; Wu, Yuan-feng1,2; Chen, Min1,2; Xing, Guo-zhen1,2; Luan, Yang2; Ren, Jin2
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| 刊名 | TOXICOLOGY LETTERS
 |
| 出版日期 | 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. |
| WOS关键词 | NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; ISOLATED RAT HEPATOCYTES ; HEPATOTOXICITY ; CELLS ; LIVER |
| 资助项目 | National Key Technologies RD Program[2008ZX09305-007] |
| WOS研究方向 | Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000264976400006 |
| 出版者 | ELSEVIER IRELAND LTD |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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