Evaluation of oxidative stress during apoptosis and necrosis caused by D-galactosamine in rat liver.
Eighteen and twenty-four hours after intraperitoneal administration of D-galactosamine (1g/kg body weight) to rats, the activity of caspase-3-like protease in the liver increased significantly compared with that in the control group given saline. Histological examinations including the in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method found apoptotic hepatocytes 18 hr after the administration of D-galactosamine. Caspase-3 activity was barely detectable in the plasma of control rats, but increased significantly 24 hr after drug administration along with a dramatic increase in glutamate-oxaloacetate transaminase (GOT). These results indicated that D-galactosamine causes apoptosis in the liver by activating caspase-3, which is released to the plasma by secondary necrosis. The concentration of lipid hydroperoxides in the liver increased significantly 24 hr after D-galactosamine administration. In contrast, the concentration of vitamin C in the liver decreased significantly 18 and 24 hr after D-galactosamine administration. These results suggest that D-galactosamine induces severe oxidative stress in the liver, leading to extensive necrosis.
Sun
Fang
F
Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
Hamagawa
Eri
E
Tsutsui
Chihiro
C
Sakaguchi
Naomi
N
Kakuta
Yuri
Y
Tokumaru
Sadako
S
Kojo
Shosuke
S
D000818:Animals; D017209:Apoptosis; D001205:Ascorbic Acid / Q000378:metabolism; D005688:Galactosamine / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000378:metabolism
D008054:Lipid Peroxides; D014810:Vitamin E; D005688:Galactosamine; D001205:Ascorbic Acid