Schisandrin B protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione redox status in mouse liver.
Previous studies in our laboratory have demonstrated the effect of Schisandrin B (Sch B),an active ingredient of the fruit of Schisandra chinensis, on enhancing the hepatic glutathione antioxidant system in mice, as evidenced by the hepatoprotection against carbon tetrachloride (CCl4) toxicity. In the present study, the mechanism involved in the hepatoprotection afforded by Sch B treatment was investigated. Treating female Balb/c mice with 1, 3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase (GRD), at a dose of 2 mmol/kg (i.p.) did not abrogate the hepatoprotective action of Sch B in CCl4-treated mice. The result indicates that the increased activity of hepatic GRD is not ascribable to the hepatoprotective action of Sch B. In control mice, the same Sch B treatment regimen caused an enhancement in hepatic mitochondrial glutathione redox status, as indicated by the significant increase and decrease in reduced and oxidized glutathione levels, respectively. While the CCl4 intoxication greatly impaired mitochondrial glutathione redox status, the beneficial effect of Sch B treatment became more evident after CCl4 challenge. Our results strongly suggest that the mechanism of hepatoprotection afforded by Sch B treatment may involve the enhancement of mitochondrial glutathione redox status.
Ip
S P
SP
Department of Biochemistry, Hong Kong University of Science & Technology, Hong Kong.
Poon
M K
MK
Che
C T
CT
Ng
K H
KH
Kong
Y C
YC
Ko
K M
KM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D034242:Cyclooctanes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D017705:Lignans; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011083:Polycyclic Compounds / Q000494:pharmacology*
D000975:Antioxidants; D034242:Cyclooctanes; D004791:Enzyme Inhibitors; D005609:Free Radicals; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D002251:Carbon Tetrachloride; D005980:Glutathione Reductase; D000410:Alanine Transaminase; D005978:Glutathione; D019803:Glutathione Disulfide