| Hepatic cytochrome p450s metabolize aristolochic acid and reduce its kidney toxicity | |
| 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 | |
| 刊名 | Kidney international
 |
| 2008-06-01 | |
| 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 |
| 通讯作者 | J ren(jungu@wadsworth.org) |
| 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 |
| WOS研究方向 | Urology & Nephrology |
| WOS类目 | Urology & Nephrology |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000255897400006 |
| 内容类型 | 期刊论文 |
| URI标识 | http://www.corc.org.cn/handle/1471x/2385572 |
| 专题 | 中国科学院大学 |
| 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. |
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