title: Hepatoprotective action of schisandrin B against carbon tetrachloride toxicity was mediated by both enhancement of mitochondrial glutathione status and induction of heat shock proteins in mice.
abstract: In the present study, we investigated the differential role of the mitochondrial glutathione status and induction of heat shock proteins (HSPs) 25/70 in protecting against carbon tetrachloride (CCl_4) hepatotoxicity in schisandrin B (Sch B)-pretreated mice. The time-course of Sch B-induced changes in these hepatic parameters were examined. Dimethyl diphenyl bicarboxylate (DDB), a non-hepatoprotective analog of Sch B, was studied for comparison. Sch B treatment (2 mmol/kg) produced maximal enhancement in hepatic mitochondrial glutathione status as well as increases in hepatic HSP 25/70 levels at 24 h post-dosing. The stimulatory effect of Sch B then gradually subsided, but the activities of hepatic mitochondrial glutathione reductase (GR) and glutathione S-transferases (GST) as well as the level of HSP 25 remained relatively high even at 72 h post-dosing. CCl_4 challenge caused significant impairment in mitochondrial glutathione status and a decrease in HSP 70 level, but the HSP 25 level was significantly elevated. While the extent of hepatoprotection afforded by Sch B pretreatment against CCl_4 was found to inversely correlate with the time elapsed after the dosing, the protective effect was associated with the ability of Sch B to maintain the mitochondrial glutathione status and/or induce further production of HSP 25 in CCl_4-intoxicated condition. On the other hand, DDB treatment (2 mmol/kg), which did not increase mitochondrial GSH level and GST activity or induce further production of HSP 25 after CCl_4 challenge, could not protect against CCl_4 toxicity. The results suggest that the enhancement of mitochondrial glutathione status and induction of HSP 25/70 may contribute independently to the hepatoprotection afforded by Sch B pretreatment.
authors.affiliation: Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Man Ho
authors.initials: MH
authors.lastname: Tang
authors.forename: Po Yee
authors.initials: PY
authors.lastname: Chiu
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control; D034242:Cyclooctanes / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D034242:Cyclooctanes; D006360:Heat-Shock Proteins; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D002251:Carbon Tetrachloride; D005978:Glutathione