Protective effect of apigenin on methotrexate-induced oxidative stress in mice

The aim of this study was to investigate the protective effect of apigenin (Apig) against oxidative damage induced by methotrexate (MTX) in mice. A total of 48 CD-1 male mice, 12 in each group, were used in the study. Mice were given ad libitum pellet feed and water. In the study, 4 groups were formed as control, MTX, Apig and Apig + MTX. The control group received 0.9% NaCl (2 mg/kg b.w) containing 0.1% dimethylsulfoxide (DMSO) intraperitoneally (i.p) for 4 days. Apigenin group received 3 mg/kg/b.w/day i.p (dissolved in DMSO) apigenin for 4 days and methotrexate group was given a single dose of 20 mg/kg/b.w/day i.p methotrexate (dissolved in 0.9% NaCl) on the 4th day. Apig+MTX group was given 3 mg/kg/b.w/day p.i Apig for 7 days and single dose 20 mg/kg/b.w MTX on 4th day. Blood, liver and kidney samples were taken at the end of the study. In serum samples, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine, in hemolysates, liver and kidney homogenates catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels and in plasma, liver and kidney homogenates MDA and SOD levels were measured. Histopathological examinations of liver and kidney samples were also performed. In the study, when MTX group was compared with the control group, there was a significant increase (p<0.05) in serum AST and ALT levels and creatinine values. In Apig+MTX group, there was a significant decrease (p<0.05) in AST, ALT and creatinine values compared with the MTX group. In MTX group, a significant increase (p<0.05) in MDA levels was found in blood, liver and kidney tissue samples compared to the control group; SOD, CAT and GSH-Px enzymes and GSH levels decreased significantly (p<0.05). In the group in which Apig + MTX was administered together, a significant decrease (p<0.05) in the amount of MDA that was increased when MTX was administered alone; SOD, CAT and GSH-Px enzymes and GSH levels increased significantly (p<0.05). In addition, histopathological examinations revealed that MTX caused marked pathological lesions in liver and kidney tissues and Apig corrected these lesions. As a result, it was found that MTX caused lipid peroxidation in blood, liver and kidney tissues and depletion of antioxidant defense systems, Apig decreased lipid peroxidation caused by MTX and showed corrective effect on antioxidant enzymes/systems. Keywords: Apigenin, Methotrexate, Mouse, Oxidative stress