Induction of P450 1A by 3-methylcholanthrene protects mice from aristolochic acid-I-induced acute renal injury
文献类型：期刊论文
| 作者 | Xue, Xiang1,2; Xiao, Ying1,2; Zhu, Hongli3; Wang, Hui1; Liu, Yongzhen1 ; Xie, Tianpei3; Ren, Jin1
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| 刊名 | NEPHROLOGY DIALYSIS TRANSPLANTATION
 |
| 出版日期 | 2008-10 |
| 卷号 | 23期号:10页码:3074-3081 |
| 关键词 | aristolochic acid nephropathy P450 1A 3-methylcholanthrene |
| ISSN号 | 0931-0509 |
| DOI | 10.1093/ndt/gfn262 |
| 文献子类 | Article |
| 英文摘要 | Background. Cytochrome P450 1A, an enzyme known to metabolize polycyclic aromatic hydrocarbons (PAHs), participates in the metabolism of aristolochic acid I (AAI) in liver and kidney microsomes isolated from humans and rodents. This study was designed to investigate whether P450 1A plays a role in AAI-induced renal injury in C57BL/6 mice. Methods. Separate groups of mice were given AAI (10 mg/kg and 20 mg/kg) or pretreatment with 3-methylcholanthrene (3-MC, an agent known to induce P450 1A expression in many species including rodents) at 60 mg/kg given at 24 h before AAI injection. Renal function and histopathology were determined at the 3rd day following the high dose of AAI and at the 14th day following the low dose of AAI treatment. For both doses, we determined in vivo AAI clearances and pharmacokinetic parameters. We also determined in vitro P450 1A1/2 activity and the ability of liver microsomes from 3-MC-treated and vehicle-treated mice to metabolize AAI. Finally, the effect of 3-MC on protein levels of P450 1A1/2 in both liver and kidney was measured by western blotting. Results. Pretreatment with 3-MC greatly protected mice against renal failure induced by AAI. In vivo AAI clearance was more rapid in 3-MC-pretreated mice than in the vehicle-pretreated mice. In addition, the P450 1A1/2 activity and the ability to metabolize AAI in hepatic microsomes isolated from 3-MC-treated mice were much greater than in vehicle-treated mice. Western blotting showed that protein levels of hepatic P450 1A1/2 were greatly increased in 3-MC-treated mice than in vehicle-treated mice. Conclusion. These results demonstrated that the induction of hepatic P450 1A1/2 protected against AAI-induced kidney injury through faster in vivo clearance of AAI and suggested an important role for hepatic P450s in the detoxification of AAI-induced renal injury. |
| WOS关键词 | CHINESE HERBS NEPHROPATHY ; INTERSTITIAL FIBROSIS ; UROTHELIAL CARCINOMA ; REDUCTIVE ACTIVATION ; FANCONIS-SYNDROME ; CYTOCHROME-P450 ; DNA ; FAILURE ; ADDUCTS ; TOXICITY |
| 资助项目 | National Grand Fundamental Research 973 Program of China[2006CB504700] |
| WOS研究方向 | Transplantation ; Urology & Nephrology |
| 语种 | 英语 |
| WOS记录号 | WOS:000259330500010 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272798]  |
| 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 新药研究国家重点实验室 |
| 通讯作者 | Ren, Jin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China; 3.Shanghai TenGen Biomed Co, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xue, Xiang,Xiao, Ying,Zhu, Hongli,et al. Induction of P450 1A by 3-methylcholanthrene protects mice from aristolochic acid-I-induced acute renal injury[J]. NEPHROLOGY DIALYSIS TRANSPLANTATION,2008,23(10):3074-3081. |
| APA | Xue, Xiang.,Xiao, Ying.,Zhu, Hongli.,Wang, Hui.,Liu, Yongzhen.,...&Ren, Jin.(2008).Induction of P450 1A by 3-methylcholanthrene protects mice from aristolochic acid-I-induced acute renal injury.NEPHROLOGY DIALYSIS TRANSPLANTATION,23(10),3074-3081. |
| MLA | Xue, Xiang,et al."Induction of P450 1A by 3-methylcholanthrene protects mice from aristolochic acid-I-induced acute renal injury".NEPHROLOGY DIALYSIS TRANSPLANTATION 23.10(2008):3074-3081. |
入库方式： OAI收割
来源：上海药物研究所
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