Evaluation of oxidative stress based on lipid hydroperoxide, vitamin C and vitamin E during apoptosis and necrosis caused by thioacetamide in rat liver.
After 12 h of thioacetamide (500 mg/kg body weight) administration to rats, the activity of caspase-3-like protease in the liver increased significantly compared to that in the control group. In plasma, the activity of caspase-3 was barely detectable in the control rat, but had increased significantly after 24 h of drug administration along with a dramatic increase in GOT. These results indicate that thioacetamide causes apoptosis in the liver by activating caspase-3, which is released to plasma by successive necrosis. At 24 h, the concentration of liver lipid hydroperoxides, a mediator of radical reaction, was 2.2 times as high as that of control rats. After 12 and 24 h of thioacetamide administration, the liver concentrations of vitamins C and E decreased significantly. The decrease of antioxidants and formation of lipid hydroperoxides 24 h after thioacetamide administration support the view that extensive radical reactions occur in the liver during the necrotic process.
Sun
F
F
Department of Food Science and Nutrition, Nara Women's University, Nara, Japan.
Hayami
S
S
Ogiri
Y
Y
Haruna
S
S
Tanaka
K
K
Yamada
Y
Y
Tokumaru
S
S
Kojo
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000096:biosynthesis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000494:pharmacology / Q000633:toxicity*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000378:metabolism*
D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D013853:Thioacetamide; D014810:Vitamin E; D001219:Aspartate Aminotransferases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D001205:Ascorbic Acid