Anti-apoptotic and Hepatoprotective Effects of Gomisin A on Fulminant Hepatic Failure Induced by D-Galactosamine and Lipopolysaccharide in Mice

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This study examined the effects of gomisin A, a lignan compound from Schisandra fructus, on <sc>D</sc>-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic apoptosis and liver failure. Mice were given an intraperitoneal injection of GalN (700 mg/kg)/LPS (10 μg/kg). Gomisin A (25, 50, 100, and 200 mg/kg) was administered intraperitoneally 1 h before the GalN/LPS injection. The liver injury was assessed biochemically and histologically. GalN/LPS increased the serum aminotransferase levels and lipid peroxidation but decreased the reduced glutathione level. The pretreatment with gomisin A attenuated these changes in a dose-dependent manner. The survival rate of the gomisin A group was significantly higher than that of the control. The mitochondria isolated after the mice had been injected with GalN/LPS were swollen, which was attenuated by the gomisin A pretreatment. The elevation of serum tumor necrosis factor-α and activation of caspase-3 were observed in the GalN/LPS group, which was attenuated by gomisin A. The gomisin A–pretreated groups showed significantly fewer apoptotic (TUNEL-positive) cells and DNA fragmentation as compared with the GalN/LPS mice. The liver protection afforded by gomisin A is the result of the reduced oxidative stress and its anti-apoptotic activity.
社団法人日本薬理学会の論文
2008-02-20