Inhibition of CYP1A1 Alleviates Colchicine-Induced Hepatotoxicity

Author:

Huang Ruoyue1,Duan Jingyi1,Huang Wen2,Cheng Yan13,Zhu Beiwei45,Li Fei16

Affiliation:

1. Department of Gastroenterology & Hepatology, Laboratory of Metabolomics and Drug-Induced Liver Injury, State Key Laboratory of Biotherapy, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China

2. Laboratory of Ethnopharmacology, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610041, China

3. Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang 330004, China

4. School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China

5. National Engineering Research Center of Seafood, Dalian 116034, China

6. State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, China

Abstract

Colchicine, a natural compound extracted from Colchicum autumnale, is a phytotoxin, but interestingly, it also has multiple pharmacological activities. Clinically, colchicine is widely used for the treatment of gouty arthritis, familial Mediterranean fever, cardiovascular dysfunction and new coronary pneumonia. However, overdose intake of colchicine could cause lethal liver damage, which is a limitation of its application. Therefore, exploring the potential mechanism of colchicine-induced hepatotoxicity is meaningful. Interestingly, it was found that CYP1A1 played an important role in the hepatotoxicity of colchicine, while it might also participate in its metabolism. Inhibition of CYP1A1 could alleviate oxidative stress and pyroptosis in the liver upon colchicine treatment. By regulating CYP1A1 through the CASPASE-1-GSDMD pathway, colchicine-induced liver injury was effectively relieved in a mouse model. In summary, we concluded that CYP1A1 may be a potential target, and the inhibition of CYP1A1 alleviates colchicine-induced liver injury through pyroptosis regulated by the CASPASE-1-GSDMD pathway.

Funder

National Key Research and Development Program of China

Publisher

MDPI AG

Subject

Health, Toxicology and Mutagenesis,Toxicology

Reference45 articles.

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