OBJECTIVE To explore the toxicological mechanism of drug-induced liver injury(DILI)in rats induced by cantharidin(CTD).METHODS SD rats were exposed to different doses of CTD(0.061 4,0.092 1,0.184 1 mg·kg-1)by oral gavage for 28 d.Liver index and serum liver function indictors were detected.HE staining was used to evaluate the pathological changes of liver.Then the proteins in endoplasmic reticulum stress(ERS),autophagy,and apoptosis-pathway were detected by Western blotting.RESULTS The liver index was increased in CTD groups.The ALT,AST,LDH,ALP and T-Bil were increased by CTD with a dose-dependent manner.Disrupted hepatic architecture and dilatation of central vein were observed after CTD intervention.The protein expression levels of GRP78,CHOP,ATF4,Beclin-1,LC3,Caspase-3,Caspase-8,and Bax/Bcl-2 were increased after CTD intervention.Molecular docking results revealed that GRP78,ATF4,and Beclin-1 could directly interconnect with CTD.CONCLUSION CTD can activate ERS,autophagy and synergistically inducing downstream apoptosis in rat,providing a novel insight into the mechanism of CTD-induced DILI.
维普
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