Abstract
Methotrexate (Metho) is cytotoxic drug widely used to treat malignant (lymphoma, leukemia, breast cancer) and non-malignant (rheumatic arthritis) diseases. It mediates nephrotoxicity via cellular oxidative stress. Pomegranate juice (POJ) has a potent antioxidant property. This research aimed to assess the potential protective effect of POJ against Metho-induced renal damage in rats. Renal toxicity was induced through intraperitoneal (ip) injection with a single dose of Metho (20 mg/kg). Forty male rats were randomly segregated into 4 groups; each group contained 10 rats. Control (Cont); Metho: rats on the 23rd day injected ip with Metho; POJ (2 ml/kg) +Metho: rats given POJ (2 ml/kg) orally once a day, and on the 23th day injected with Metho ip; and POJ (4 ml/kg) + Metho: rats given POJ (4 ml/kg) orally once a day, and on the 23th day rats were injected with Metho ip. After 5 days of Metho ip. injection, blood samples and renal tissue were obtained. Serum renal functions, ionic electrolytes (sodium and potassium), and pro-inflammatory cytokines were analyzed. Renal oxidative stress and antioxidant enzymes were also measured. Renal tissue were examined microscopically. Metho caused a significant increase in serum renal functions and disturbance in ionic electrolytes. As well as, there was a significant increase in pro-inflammatory cytokines and oxidative stress parameters, with detectable degenerative alteration in glomerulus and renal tissue changes compared with the Cont group. Pretreatment with POJ resulted in preventing biochemical and histopathological alterations induced by Metho. The high dose of POJ (4 ml/kg) was significantly more effective than low dose (2 ml/kg). In conclusion, POJ exerted a potent nephroprotective action and prevent Metho-induced nephrotoxicity. Therefore, POJ may has a beneficial effect in patients receiving Metho therapy.