title: Tanshinone I protects mice from aristolochic acid I-induced kidney injury by induction of CYP1A.
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.
authors: 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.
authors: Chenchen
authors: C
authors: Feng
authors: Xiaofeng
authors: X
authors: Xie
authors: Mengjun
authors: M
authors: Wu
authors: Chunzhu
authors: C
authors: Li
authors: Man
authors: M
authors: Gao
authors: Mingxia
authors: M
authors: Liu
authors: Xinming
authors: X
authors: Qi
authors: Jin
authors: J
authors: Ren
mesh_terms: D045784:Abietanes / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D034341:Aristolochic Acids / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D001774:Blood Chemical Analysis; D015153:Blotting, Western; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D013056:Spectrophotometry, Ultraviolet
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D034341:Aristolochic Acids; D002273:Carcinogens; C021751:tanshinone; D012313:RNA; C000228:aristolochic acid I; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2
keywords: Aristolochic acid; CYP1A; Kidney injury; Tanshinone I