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Oxidative Stress In Paracetamol Induced Pathogenesis Of Liver Damage

Premila Abraham, Banumathi Ramakrishna

Oxidative damage to hepatocellular proteins in paracetamol (acetaminophen)- induced liver damage was studied in phenobarbitone-pretreated Wistar rats, at a dose of 1gm per kg body wt in dimethyl sulphoxide after 4 hours, 24 hours and 48 hrs of administration. Protein carbonyl content, protein thiol, nonprotein thiol and lipid peroxide levels were measured in the liver as indicators of oxidative stress. The activities of important thiol dependant enzymes, glutamine synthetase and glyceraldehyde- 3-phosphate dehydrogenase (GAPDH) in the liver were also assayed. Protein thiol and albumin were measured in the plasma along with alanine aminotransferase (ALT) activity. Significant oxidative damage to hepatocellular proteins and lipids at 24 hrs was evident with approximately 10 fold increase in serum alanine aminotransferase activity, and perivenular necrosis, histologically. Nonprotein thiol (mainly glutathione) was decreased by 50% in the livers of acetaminophen-treated rats. Protein carbonyls content, protein thiol, plasma albumin and lipid peroxide levels were increased and the activities of glutamine synthase and GAPDH activity were decreased in acetaminophen-treated rats as compared to the controls. The present study suggests that oxidative damage to hepatocellular proteins and lipids occurs after acetaminophen intoxication in rats, and that it may contribute to the pathogenesis of liver damage.