title: Dioscin, a natural steroid saponin, shows remarkable protective effect against acetaminophen-induced liver damage in vitro and in vivo.
abstract: The aim of the study was to investigate the protective effect of dioscin against APAP-induced hepatotoxicity. In the in vitro tests, HepG2 cells were given APAP pretreatment with or without dioscin. In the in vivo experiments, mice were orally administrated dioscin for five days and then given APAP. Some biochemical and morphology parameters were assayed and the possible mechanism was investigated. Dioscin improved AST release, mitochondrial dysfunction, apoptosis and necrosis of HepG2 cells induced by APAP. Following administration of dioscin, APAP-induced hepatotoxicity in mice was significantly attenuated. Furthermore, the liver cell apoptosis and necrosis, and hepatic mitochondrial edema were also prevented. Fifteen differentially expressed proteins were found by using proteomics, and six of them, Suox, Krt18, Rgn, Prdx1, MDH and PNP were validated. These proteins may be involved in the hepatoprotective effect of dioscin and might cooperate with the levels of Ca(2+) in mitochondria, decreased expression of ATP2A2, and decreased mitochondrial cardiolipin. In addition, dioscin inhibited APAP-induced activation and expression of CYP2E1, up-regulated the expression of Bcl-2 and Bid, and inhibited the expression of Bax, Bak and p53. Dioscin showed a remarkable protective effect against APAP-induced hepatotoxicity by adjusting mitochondrial function. These results indicated that dioscin has the capability on the treatment of liver injury.
authors.affiliation: College of Pharmacy, Dalian Medical University, 9 Western Lvshun South Road, Dalian 116044, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Cong
authors.forename: Lingli
authors.initials: L
authors.lastname: Zheng
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001688:Biological Products / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D020552:Comet Assay; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001688:Biological Products; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D000082:Acetaminophen; C019357:dioscin; D004144:Diosgenin