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Background: Chlorpromazine has an effectively and extensive use for treated psychotic upset such as manicdepression or schizophrenia in adults, besides used to treat nausea, vomiting and anxiety, there is limitation in therapeutic use because of induction hepatotoxicity. Recently reports have been advocate that ability of supplementation with antioxidant can be influence chlorpromazine promote acute liver injury. Objectives: The current study aims mainly to investigate the prophylactic effect of oral treated with Tocopheronic acid against the liver damage induced by intraperitoneal administration of chlorpromazine. Method: Efficacy of Tocopheronic acid against the hepatotoxicity was evaluated in terms of biochemical estimation like serum level LDH, ALT and AST and of GSH antioxidant related enzyme activity like GST, GPx, SOD, GR, Catalase, QR and 1-GGT) level, with histopathological changes. Results: In treated group chlorpromazine induced glutathione depletion, oxidase activity, lipid peroxidation, xanthine, depletion in antioxidant (superoxide dismutase, glutathione, reductase, glutathione peroxidase, catalase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (quinine reductase and glutathione-S-transferase) enzyme activities significantly (p<0.05) when compared with the control, and hepatic tissue damage group which induced by chlorpromazine. The findings from histological changes supported the predication that Tocopheronic acid can be mitigation chlorpromazine induced acute liver injury. Conclusion: The data of the current study elucidate that oxidative stress and liver damage are closely connected with chlorpromazine induced injury and Tocopheronic acid shows the protective efficacy against chlorpromazine induce liver toxicity; it may be possible through reducing the free radicals and inflammatory reaction. [ABSTRACT FROM AUTHOR]