Anti-apoptotic and hepatoprotective effects of gomisin A on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice.
This study examined the effects of gomisin A, a lignan compound from Schisandra fructus, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic apoptosis and liver failure. Mice were given an intraperitoneal injection of GalN (700 mg/kg) / LPS (10 microg/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-alpha 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.
Kim
Sung-Hwa
SH
College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea.
Kim
Yeong Shik
YS
Kang
Sam Sik
SS
Bae
Kihwan
K
Hung
Tran Manh
TM
Lee
Sun-Mee
SM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000097:blood; D034242:Cyclooctanes / Q000627:therapeutic use*; D053938:DNA Fragmentation; D004149:Dioxoles / Q000627:therapeutic use*; D005688:Galactosamine; D005978:Glutathione / Q000378:metabolism; D017705:Lignans / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D017093:Liver Failure / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D008070:Lipopolysaccharides; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; C033585:schizandrol B; D005688:Galactosamine; D000410:Alanine Transaminase; D053148:Caspase 3; D005978:Glutathione