Literature DB >> 23981375

Tanshinone I protects mice from aristolochic acid I-induced kidney injury by induction of CYP1A.

Chenchen Feng1, Xiaofeng Xie, Mengjun Wu, Chunzhu Li, Man Gao, Mingxia Liu, Xinming Qi, Jin Ren.   

Abstract

Hepatic CYP1A especially CYP1A2 plays an important role in the reduction of aristolochic acid I (AAI) nephrotoxicity. In this study, we investigated the effects of tanshinone I, a strong inducer of Cyp1a, on the nephrotoxicity induced by AAI. Histopathology and blood biochemistry assays showed that tanshinone I could reduce AAI-induced acute kidney injury. Pharmacokinetics analysis revealed that tanshinone I markedly decreased AUC of AAI in plasma and the content of AAI in both liver and kidney, indicating the enhancement of AAI metabolism. Real-time PCR and Western blot analysis confirmed that tanshinone I effectively increased the mRNA and protein levels of hepatic CYP1A1 and CYP1A2 in vivo. Luciferase assay showed that tanshinone I strongly increased the transcriptional activity of CYP1A1 and CYP1A2 in the similar extent. In summary, our data suggested that tanshinone I facilitated the metabolism of AAI and prevented AAI-induced kidney injury by induction of hepatic CYP1A 1/2 in vivo.
Copyright © 2013 Elsevier B.V. All rights reserved.

Entities:  

Keywords:  Aristolochic acid; CYP1A; Kidney injury; Tanshinone I

Mesh:

Substances:

Year:  2013        PMID: 23981375     DOI: 10.1016/j.etap.2013.07.017

Source DB:  PubMed          Journal:  Environ Toxicol Pharmacol        ISSN: 1382-6689            Impact factor:   4.860


  13 in total

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