Analysis of the metabolic mechanism in Cantharidin-induced hepatotoxicity in LO2 cells using lipidomics analysis  

作　　者：Jian-Yong Zhang Fang Liu Tian-Mu He Qi-Yi Wang Yan Zhang Xiao-Yan Yuan Xiao-Fei Li Can-Can Duan 

机构地区：[1]Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi 563000,China.2Department of Pharmacy,Zunyi Medical University,Zunyi,Guizhou 563000,China.3School of Basic Medical Sciences,Zunyi Medical University,Zunyi 563000,China.

出　　处：《Asian Toxicology Research》2021年第2期14-24,共11页

基　　金：The National Natural Science Foundation of China(Grants no.81760746 and 81803838);Education Department of Guizhou Province of China(GNYL[2017]006);Provincial Department of Education youth talent support program(qiankehe KY[2017]078);Guizhou Provincial Science&Technology“125-Plan”Major Project([2015]039).

摘　　要：Background:Cantharidin is a major active compound from Banmao(Mylabris).Cantharidin has obvious anticancer activity.However,its clinical application is limited due to serious hepatotoxicity.Methods:To evaluate the toxicity of human liver LO2 cells exposed to cantharidin by lipidomics.After exposing LO2 cells to different doses of cantharidin,the metabolites in LO2 cells were analyzed by nontargeted lipidomics based on liquid chromatography-mass spectrometry.Partial least-squares discriminant analysis and orthogonal partial least-squares discriminant analysis were used to screen differentially expressed metabolites,and then the main metabolic pathways were analyzed.Results:Pattern recognition analysis showed that the lipid metabolite profiles were changed significantly after cantharidin treatment,and 39 differential lipid metabolites were found.Additional analysis showed that these metabolites could mainly involve the metabolic pathways of triglyceride and acylcarnitine for cantharidin toxicity to LO2 cells.Conclusion:Cantharidin has obvious toxic effects on LO2 cells from the perspective of lipid metabolism.Moreover,the LO2 cytotoxicity induced by cantharidin is mainly related to the disorder of triglyceride and acylcarnitine metabolism.It can provide a scientific basis for cantharidin-induced hepatotoxicity.

关 键 词：Hepatoxicity CANTHARIDIN LC-MS LIPIDOMICS 

分 类 号：R73[医药卫生—肿瘤]