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Background: Methotrexate (MTX) is widely used as a cytotoxic chemotherapeutic agent for malignancies as well as in the treatment of various inflammatory diseases. MTX treatment has been associated with hepatic toxicity and genotoxicity. The current study was conducted to assess the potential protective role of N-acetylcysteine in attenuation of methotrexate–induced hepatic damage and genotoxicity in MTX intoxicated male albino rats. Methods: Forty, apparently healthy adult male albino rats weighed 150+10 gm were randomly divided into four groups; [group 1: negative control group, group 2: positive control (NAC treated) group, group 3: MTX treated group, group 4: MTX/NAC treated group]. The rats were treated once daily for 12 weeks by I.V injection of Methotrexate in a dose of 2 mg/kg (1 /7 LD50) and N-acetylcysteine in a dose of 80 mg/kg (1 /14 LD50) in the tail veins of rats. Blood samples were obtained at the end of the 4th, 8th and 12th weeks and were prepared for ALT levels and BAX gene expression value examination. At the end of the study, liver samples were obtained for histopathological examination. Results: A significant constant increase in ALT levels and BAX gene expression value of the MTX-treated group (group 3) was observed throughout the study. Supplementation of NAC concomitantly with MTX in group 4 reduced significantly ALT levels and BAX gene expression value when compared to the non-supplemented group 3 that treated with MTX at the 4th, 8th and 12th weeks (P< 0.000).The previous chemical results were confirmed by the histopathological studies of the liver that revealed the presence of dilatation and congestion of the central veins, hepatic sinusoids, hepatic arteries, portal veins with increased number of Kupffer cells and pyknosis of the hepatic nuclei in group 3: MTX treated group. On the other hand, the liver sections showed the normal hepatic architectures with addition of NAC with MTX in group 4. Conclusion: The present study showed that NAC has a good protective effect against the hepatic damage and genotoxicity induced by MTX in male albino rats.

N-ACYTEL CYSTEINE AMELIORATES METHOTREXATE INDUCED HEPATIC TOXICITY AND GENOTOXICITY IN MALE ALBINO RATS