Baicalin Protects Mice from Aristolochic Acid I-Induced Kidney Injury by Induction of CYP1A through the Aromatic Hydrocarbon Receptor

doi:10.3390/ijms160716454

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	Baicalin Protects Mice from Aristolochic Acid I-Induced Kidney Injury by Induction of CYP1A through the Aromatic Hydrocarbon Receptor
	Wang, Ke 2; Feng, Chenchen 1; Li, Chenggang 1; Yao, Jun 1; Xie, Xiaofeng 1; Gong, Likun1 ; Luan, Yang 1; Xing, Guozhen 1; Zhu, Xue 2; Qi, Xinming1
刊名	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
	2015-07
卷号	16 期号:7 页码:16454-16468
关键词	aristolochic acid kidney injury baicalin aromatic hydrocarbon receptor CYP1A
ISSN号	1422-0067
DOI	10.3390/ijms160716454
文献子类	Article
英文摘要	Exposure to aristolochic acid I (AAI) can lead to aristolochic acid nephropathy (AAN), Balkan endemic nephropathy (BEN) and urothelial cancer. The induction of hepatic CYP1A, especially CYP1A2, was considered to detoxify AAI so as to reduce its nephrotoxicity. We previously found that baicalin had the strong ability to induce CYP1A2 expression; therefore in this study, we examined the effects of baicalin on AAI toxicity, metabolism and disposition, as well as investigated the underlying mechanisms. Our toxicological studies showed that baicalin reduced the levels of blood urea nitrogen (BUN) and creatinine (CRE) in AAI-treated mice and attenuated renal injury induced by AAI. Pharmacokinetic analysis demonstrated that baicalin markedly decreased AUC of AAI in plasma and the content of AAI in liver and kidney. CYP1A induction assays showed that baicalin exposure significantly increased the hepatic expression of CYP1A1/2, which was completely abolished by inhibitors of the Aromatic hydrocarbon receptor (AhR), 3',4'-dimethoxyflavone and resveratrol, in vitro and in vivo, respectively. Moreover, the luciferase assays revealed that baicalin significantly increased the luciferase activity of the reporter gene incorporated with the Xenobiotic response elements recognized by AhR. In summary, baicalin significantly reduced the disposition of AAI and ameliorated AAI-induced kidney toxicity through AhR-dependent CYP1A1/2 induction in the liver.
资助项目	National Natural Science Foundation[81300787] ; Natural Science Foundation of Jiangsu Province[BK2011168] ; Natural Science Foundation of Jiangsu Province[BK2012105] ; Natural Science Foundation of Jiangsu Province[BK20141103] ; Major Project of Wuxi Municipal Health Bureau[ZS201401]
WOS关键词	CYTOCHROMES P450 1A1/2 ; BETA-NAPHTHOFLAVONE ; CHINESE HERBS ; TOXICITY ; DETOXICATION ; REDUCTASE ; DISEASE ; CANCER ; 1A2 ; BIOACTIVATION
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI AG
WOS记录号	WOS:000359900100118
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276473]
专题	药物安全性评价中心
通讯作者	Qi, Xinming
作者单位	1.Chinese Acad Sci, Grad Sch, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China 2.Jiangsu Inst Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Key Lab Nucl Med, Wuxi 214063, Jiangsu, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Ke,Feng, Chenchen,Li, Chenggang,et al. Baicalin Protects Mice from Aristolochic Acid I-Induced Kidney Injury by Induction of CYP1A through the Aromatic Hydrocarbon Receptor[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2015,16(7):16454-16468.
APA	Wang, Ke.,Feng, Chenchen.,Li, Chenggang.,Yao, Jun.,Xie, Xiaofeng.,...&Ren, Jin.(2015).Baicalin Protects Mice from Aristolochic Acid I-Induced Kidney Injury by Induction of CYP1A through the Aromatic Hydrocarbon Receptor.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,16(7),16454-16468.
MLA	Wang, Ke,et al."Baicalin Protects Mice from Aristolochic Acid I-Induced Kidney Injury by Induction of CYP1A through the Aromatic Hydrocarbon Receptor".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 16.7(2015):16454-16468.