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
Issue title: Proceedings of the Second International
Symposium on Antioxidants in Nutrition and Therapy, Bali, Indonesia, 2–4
October 2002
Affiliations: Department of Biochemistry, The Hong Kong University
of Science & Technology, Clear Water Bay, Hong Kong SAR, China
Note: [] Address for correspondence: Dr. Kam Ming Ko, Department of
Biochemistry, The Hong Kong University of Science & Technology, Clear
Water Bay, Hong Kong, China. Tel.: 852 2358 7298; Fax: 852 2358 1552; E-mail:
bcrko@ust.hk
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.
