The Effects of Pomegranate (Punica granatum L.) Peel Methanolic Extract on Methotrexate Induced Changes in Hepatic Antioxidant Enzymes of Rats

Abstract

Background: Methotrexate (MTX), as one of the most pivotal drugs in treatment of some malignancies and autoimmune diseases, is associated with damages to different tissues particularly the liver tissue through impairing the balance between antioxidant and pro-oxidants. Pomegranate peel is a great source of polyphenols with antioxidant function that has recently become a center of attention. Objectives: The current study was undertaken to investigate the effects of MTX and pomegranate peel methanolic extract (PPME), alone and in combination, on liver antioxidants of rats. Methods: Antioxidant capacity, total phenolic and flavonoid contents of PPME were analyzed. 32 rats were divided into (1) control, (2) orally received 500 mg/kg PPME, (3) intramuscularly received 10 mg/kg MTX, and (4) PPME (for 18 days) and MTX (for 3 days beginning from the 10th day) groups. After the experimental period, the rats were euthanatized and tissue samples were obtained for antioxidant analysis. Results: PPME had a considerable antioxidant capacity, as well as total phenolic and flavonoid contents. There were low liver contents of Glutathione peroxidase (GPx) and Catalase and a high level of Malondialdehyde and Superoxide dismutase (SOD) in the Methotrexate group compared to the control group (P < 0.05). In the Methotrexate-PPME group, PPME could increase the GPx and Catalase contents and decrease the SOD content of the liver compared to the Methotrexate group. GPx of liver samples in the PPME group decreased (P < 0.05). GPx decreased and Malondialdehyde increased in the Methotrexate-PPME group compared to the control group (P < 0.05). Conclusions: Methotrexate can surprisingly increase SOD and Malondialdehyde and decrease Catalase contents. PPME can decrease GPx and relatively prevent the effects of Methotrexate on SOD and Catalase contents of the liver tissue. However, further studies are recommended.