This study aimed to assess the antioxidant effects of rutin on methotrexate-induced hepatic oxidative stress. Wistar Albino rats (n=24) were separated into 4 groups: control group (C); methotrexate (M, 20 mg/kg, single dose) group; rutin (R, 50 mg/kg/day, for fifteen days) group; and methotrexate + rutin [MR, methotrexate (20 mg/kg, single dose) + rutin (50 mg/kg/day, for fifteen days)] group. Rats were sacrificed on the sixteenth day and liver tissues were removed. The liver

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... dehydrogenase (G6PD), glutathione peroxidase (GPx), malondialdehyde (MDA), nicotinamide adenine dinucleotide phosphate (NADPH), total glutathione (tGSH), and vitamin C were determined colorimetrically. Malondialdehyde increased and vitamin C decreased in the M group compared to the others (P<0.001). Total glutathione reduced in both M and MR groups compared to C group (P<0.05). An important decrease in M group NADPH and GPx compared to C group (P<0.001) was observed. Nicotinamide adenine dinucleotide phosphate of R group were determined to be higher than M group (P<0.001). In this study, it might demonstrate that methotrexate caused oxidative stress in the liver and rutin had antioxidant effects on methotrexate-induced hepatic oxidative stress. Consequently, it can be suggested that rutin may be useful in attenuating the side effects of methotrexate on the liver.