Liver Injury Induced by Cantharidin Through Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Rat

Tianmu HE; Kuan Chen; Lijuan Xiong; Kexin Lin; Dingyang LU; Xiaofei LI; Jianyong Zhang

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Liver Injury Induced by Cantharidin Through Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Rat

VernacularTitle:内质网应激、自噬与凋亡在斑蝥素致大鼠肝毒性中的作用
Author: Tianmu HE ^{1
,

2} ; Kuan CHEN ³ ; Lijuan XIONG ³ ; Kexin LIN ¹ ; Dingyang LU ³ ; Xiaofei LI ^{1
,

2} ; Jianyong ZHANG ³
Author Information

1. Zunyi Medical University School of Basic Medicine
2. School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
3. Zunyi Medical University School of Pharmacy, Key Laboratory of Basic Pharmacology Ministry Education, Joint International Research Laboratory of Ethnomedicine Ministry of Education, Zunyi 563000, China
Publication Type:Journal Article
Keywords: cantharidin; drug-induced liver injury; endoplasmic reticulum stress; autophagy; apoptosis
From: Chinese Journal of Modern Applied Pharmacy 2024;41(2):156-165
CountryChina
Language:Chinese
Abstract: 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.