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The effect of citric acid on liver and brain oxidative stress and liver tissue damage was studied. Rats were treated with thioacetamide at 300 mg/kg, intraperitoneally, for two successive days alone or together with orally administered citric acid at doses of 0.4 g/kg or 1g/kg. Rats were euthanized 24h after last treatments and their livers and brains were dissected out for determination of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1). Serum alanine aminotransferase and aspartate aminotransferase were determined and histological investigation for the liver tissue was carried out. Results showed that compared with the saline control, treatment with thioacetamine caused marked increase in liver and brain MDA and NO together with GSH depletion and inhibition of PON-1 activity. Serum aminotransferases were markedly increased in thioacetamide-treated rats. The histologic study showed distorted liver architecture, necrotic and apoptotic hepatocytes, fatty change, and ballooning degeneration. Citric acid reduced the increases in liver and brain MDA and NO contents and markedly increased GSH level and PON-1 activity. It also reduced the increments in activities of serum transaminases. These effects of citric acid were dose-dependent. Histologic examination confirmed that rats treated with citric acid at 1g/kg had markedly reduced liver damage. In conclusion, 1g/kg citric acid given at time of thioacetamide administration markedly reduced oxidative stress in both the liver and brain tissue and was able to restore liver architecture.
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