Inhibition of CYP1A1 Alleviates Colchicine-Induced Hepatotoxicity
Ruoyue Huang,
Jingyi Duan,
Wen Huang,
Yan Cheng,
Beiwei Zhu,
Fei Li
Affiliations
Ruoyue Huang
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
Jingyi Duan
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
Wen Huang
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
Yan Cheng
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
Beiwei Zhu
School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
Fei Li
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
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.
