| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2583079 | Environmental Toxicology and Pharmacology | 2013 | 8 Pages |
•Tanshinone I facilitated the metabolism of AAI and reduced AAN.•Tanshinone I induced liver CYP1A expression.•Tanshinone I similarly increased the transcriptional activity of CYP1A1 and 1A2.
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.
