Effects of schisandrin B enantiomers on cellular glutathione and menadione toxicity in AML12 hepatocytes.
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.
Chiu
Po Yee
PY
Department of Biochemistry, Hong Kong University of Science and Technology, SAR, China.
Leung
Hoi Yan
HY
Poon
Michel K T
MK
Mak
Duncan H F
DH
Ko
Kam Ming
KM
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*
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