title: Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways.
abstract: Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP-) induced liver injury in a mice model.Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activities, and liver histopathological changes were examined. The MAP kinases were also detected by western blotting.Results. Our results showed that tropisetron pretreatment significantly attenuated the acute elevations of the liver enzyme ALT level, hepatic MPO activity, and hepatocytes necrosis in a dose-dependent manner (0.3-10 mg/kg) in APAP-induced hepatotoxicity mice. Tropisetron (1 and 3 mg/kg) suppressed APAP-induced hepatic lipid peroxidation expression and alleviated GSH and SOD depletion. Administration of tropisetron also attenuated the phosphorylation of c-Jun-NH2-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) caused by APAP.Conclusion. Our data demonstrated that tropisetron's hepatoprotective effect was in part correlated with the antioxidant, which were mediated via JNK and ERK pathways on acetaminophen-induced liver injury in mice.
authors.affiliation: Department of Anesthesiology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.
authors.forename: Fu-Chao
authors.identifier: 0000-0003-1712-4053
authors.initials: FC
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.
authors.forename: Hung-Chen
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.
authors.forename: Chia-Chih
authors.initials: CC
authors.lastname: Liao
authors.affiliation: Department of Anesthesiology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.
authors.forename: Allen H
authors.initials: AH
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.
authors.forename: Huang-Ping
authors.identifier: 0000-0002-3030-0560
authors.initials: HP
authors.lastname: Yu
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D000077526:Tropisetron
chemical_list: D007211:Indoles; D000082:Acetaminophen; D000077526:Tropisetron; D048670:MAP Kinase Kinase 4