Objectives: In the present study, we investigated the probably curable effects of N-acetylcysteine (NAC) on Methotrexate (MTX)-induced hepatotoxicity as biochemically and histopathologically. Methods: For this purpose 24 male rats were divided into four groups as; control, MTX, NAC+MTX and NAC groups. Control and MTX groups were given 0.09% NaCl solution for 7 days; and MTX group was administrated single dose MTX at fourth day, additionally. NAC+MTX and NAC groups were given NAC during 7 days; and NAC+MTX group was applied single dose MTX at fourth day. On the eighth day, rats were sacrificed, blood samples and livers were taken. Results: According to biochemical analysis results, NAC caused a reduction in the MTX-induced increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) enzymes. Histopathologically, cytoplasmic swelling-vacuolization, sinusoidal dilatation and congestion seen in the MTX group were decreased with NAC administration. Although abundant lipid droplets were found in the sections stained with Oil Red O of MTX, NAC usage decreased this situation to the minimum level. While NAC given with MTX decreased Bax immunopositivity, it increased Bcl-2 immunopositivity. Also, TUNEL-positive cells were less in NAC+MTX group according to MTX group. Conclusion: Findings obtained in the current study suggest that NAC may be effective on the MTX-induced hepatotoxicity. Keywords: Hepatotoxicity, histopathology, methotrexate, n-acetylcysteine, TUNEL
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