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

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

  • Environ Toxicol Pharmacol. 2013 Nov;36(3):850-7. doi: 10.1016/j.etap.2013.07.017.
Chenchen Feng 1,  Xiaofeng Xie,  Mengjun Wu,  Chunzhu Li,  Man Gao,  Mingxia Liu,  Xinming Qi,  Jin Ren
Affiliations

Affiliation

  • 1 Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences; Graduate School of the Chinese Academy of Sciences, Shanghai 201203, China.
PMID: 23981375 DOI: 10.1016/j.etap.2013.07.017
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.

Keywords

Aristolochic acid; CYP1A; Kidney injury; Tanshinone I.

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