title: Hepatoprotective mechanism of schisandrin B: role of mitochondrial glutathione antioxidant status and heat shock proteins.
abstract: In this study, the time course of schisandrin B- (Sch B-) induced changes in hepatic mitochondrial glutathione antioxidant status (mtGAS) and heat shock protein (HSP) 25/70 induction was examined to study their differential roles in the hepatoprotection afforded by Sch B pretreatment against carbon tetrachloride (CCl(4)) toxicity in mice. Dimethyl diphenyl bicarboxylate (DDB), a nonhepatoprotective analog of Sch B, was also included for comparison. The results indicate that Sch B treatment (2 mmol/kg) produced maximum enhancement in hepatic mtGAS and increases in both hepatic HSP 25 and HSP 70 levels at 24 h after dosing. While the extent of hepatoprotection afforded by Sch B pretreatment against CCl(4) was found to correlate inversely with the elapsed time postdosing, the protective effect was associated with the ability to sustain mtGAS and/or HSP 70 levels in a CCl(4)-intoxicated condition. On the other hand, DDB (2 mmol/kg) treatment, which did not sustain mtGAS and HSP 70 level, could not protect against CCl(4) toxicity. Abolition of the Sch B-mediated enhancement of mtGAS by buthionine sulfoximine/phorone did not completely abrogate the hepatoprotective action of Sch B. The results indicate that Sch B pretreatment independently enhances mtGAS and induces HSP 25/70 production, particularly under conditions of oxidative stress, thereby protecting against CCl(4) hepatotoxicity.
authors.affiliation: Department of Biochemistry, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Po Yee
authors.initials: PY
authors.lastname: Chiu
authors.forename: Man Ho
authors.initials: MH
authors.lastname: Tang
authors.forename: Duncan H F
authors.initials: DH
authors.lastname: Mak
authors.forename: Michel K T
authors.initials: MK
authors.lastname: Poon
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000494:pharmacology; D034242:Cyclooctanes / Q000494:pharmacology*; D004149:Dioxoles / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D018384:Oxidative Stress; D011083:Polycyclic Compounds / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D034242:Cyclooctanes; D004149:Dioxoles; D004791:Enzyme Inhibitors; D005609:Free Radicals; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D017705:Lignans; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011083:Polycyclic Compounds; C015499:schizandrin B; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; D000255:Adenosine Triphosphate; D002251:Carbon Tetrachloride; D005978:Glutathione