title: Effects of schisandrin B enantiomers on cellular glutathione and menadione toxicity in AML12 hepatocytes.
abstract: Effects of schisandrin B enantiomer ((+)Sch B and (-)Sch B) treatment on the reduced cellular glutathione (GSH) level and susceptibility to menadione-induced toxicity were investigated and compared in AML12 hepatocytes. (+)Sch B or (-)Sch B treatment at 6.25 micromol/l produced a time-dependent change in cellular GSH level, with the maximal stimulation occurring 16 h after dosing. (+)Sch B/(-)Sch B pretreatment for 16 h dose-dependently protected against menadione toxicity, with the maximum degree of protection observable at 6.25 micromol/l and the extent of protection afforded by (-)Sch B being larger than that of (+)Sch B. The cytoprotection was associated with a parallel enhancement in cellular GSH level in both non-menadione (control) and menadione-intoxicated cells. While the GSH depletion produced by buthionine sulfoximine/phorone treatment largely abrogated the cytoprotective action of (+)Sch B/(-)Sch B, it almost completely abolished the GSH-enhancing effect of (+)Sch B and (-)Sch B in both control and menadione-treated cells. Both (+)Sch B and (-)Sch B treatments increased the GSH reductase activity in control and menadione-treated cells, with the stimulatory action of (-)Sch B being more potent than that of (+)Sch B in the control condition. (+)Sch B and (-)Sch B also enhanced the gamma-glutamate cysteine ligase activity in menadione-intoxicated cells. The results indicate that (-)Sch B is more effective than (+)Sch B in enhancing cellular GSH and protecting against oxidant injury in hepatocytes.
authors.affiliation: Department of Biochemistry, Hong Kong University of Science and Technology, SAR, China.
authors.forename: Po Yee
authors.initials: PY
authors.lastname: Chiu
authors.forename: Hoi Yan
authors.initials: HY
authors.lastname: Leung
authors.forename: Michel K T
authors.initials: MK
authors.lastname: Poon
authors.forename: Duncan H F
authors.initials: DH
authors.lastname: Mak
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000818:Animals; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control; D034242:Cyclooctanes / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D011083:Polycyclic Compounds / Q000494:pharmacology*; D024483:Vitamin K 3 / Q000633:toxicity*
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D024483:Vitamin K 3; D007770:L-Lactate Dehydrogenase; D005980:Glutathione Reductase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione