Hepatic cytochrome P450s metabolize aristolochic acid and reduce its kidney toxicity
文献类型：期刊论文
| 作者 | Y Xiao1,2; M Ge3; X Xue1,2; C Wang2; H Wang1; X Wu1,2; L Li2 ; L Liu1,2; X Qi1,2; Y Zhang1,2
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| 刊名 | KIDNEY INTERNATIONAL
 |
| 出版日期 | 2008-06 |
| 卷号 | 73期号:11页码:1231-1239 |
| 关键词 | aristolochic acid nephropathy CYP1A CPR null mice kidney toxicity metabolism |
| ISSN号 | 0085-2538 |
| DOI | 10.1038/ki.2008.103 |
| 文献子类 | Article |
| 英文摘要 | Cytochrome P450s metabolize the naturally occurring nephrotoxin aristolochic acid. Using liver-specific cytochrome P450 reductase-null mice we found that a low but lethal dose of aristolochic acid I was ineffective in wild-type mice. Induction of hepatic CYP1A by 3-methylcholanthrene pretreatment markedly increased the survival rate of wild type mice given higher doses and these mice were protected from aristolochic acid I-induced renal injury. Clearance of aristolochic acid I in null mice was slower compared to control and the 3-methylcholanthrene-pretreated wild type mice. The levels of aristolochic acid I in the kidney and liver were much higher in null mice but much lower in 3-methylcholanthrene- treated compared to control wild type mice. Hepatic microsomes from 3-methylcholanthrenetreated wild type mice had greater activity compared to untreated mice. Finally, aristolochic acid I was more cytotoxic than its major metabolite aristolactam I and this cytotoxicity was decreased in human renal tubular epithelial HK2 cells in the presence of a reconstituted hepatic microsome-cytosol (S9) system. These results indicate that hepatic P450s play an important role in metabolizing aristolochic acid I into less toxic metabolites and thus have a detoxification role in aristolochic acid I-induced kidney injury. |
| WOS关键词 | BALKAN ENDEMIC NEPHROPATHY ; PROSTAGLANDIN-H SYNTHASE ; LIVER-SPECIFIC DELETION ; MICROSOMAL CYTOCHROME-P450 ; CHINESE HERBS ; CONDITIONAL DELETION ; UROTHELIAL CANCER ; MASS-SPECTROMETRY ; RISK-FACTOR ; NULL MOUSE |
| 资助项目 | NIA NIH HHS[AG026329] |
| WOS研究方向 | Urology & Nephrology |
| 语种 | 英语 |
| WOS记录号 | WOS:000255897400006 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272910]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | J Ren |
| 作者单位 | 1.Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China; 3.Shanghai TenGen Biomed Co, Shanghai, Peoples R China; 4.SUNY Albany, Wadsworth Ctr, New York State Dept Hlth, Albany, NY USA; 5.SUNY Albany, Sch Publ Hlth, Albany, NY USA |
| 推荐引用方式 GB/T 7714 | Y Xiao,M Ge,X Xue,et al. Hepatic cytochrome P450s metabolize aristolochic acid and reduce its kidney toxicity[J]. KIDNEY INTERNATIONAL,2008,73(11):1231-1239. |
| APA | Y Xiao.,M Ge.,X Xue.,C Wang.,H Wang.,...&J Ren.(2008).Hepatic cytochrome P450s metabolize aristolochic acid and reduce its kidney toxicity.KIDNEY INTERNATIONAL,73(11),1231-1239. |
| MLA | Y Xiao,et al."Hepatic cytochrome P450s metabolize aristolochic acid and reduce its kidney toxicity".KIDNEY INTERNATIONAL 73.11(2008):1231-1239. |
入库方式： OAI收割
来源：上海药物研究所
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