RENAL ANTIOXIDANT BIOMARKERS IN CUCURBITA PEPO SEED OIL PROPHYLAXIS OF METHOTREXATE TOXICITY IN MALE WISTAR RATS.

ABSTRACT Methotrexate is a widely used chemotherapeutic and immunosuppressive drug for the treatment of various malignancies, autoimmune disorders, and inflammatory diseases. However, its clinical use is often limited by severe adverse effects, particularly nephrotoxicity, which is largely associated with oxidative stress and depletion of renal antioxidant defense systems. Natural products rich in antioxidant compounds have gained increasing attention as potential protective agents against drug-induced organ toxicity. Cucurbita pepo seed oil is known to contain bioactive phytochemicals such as tocopherols, carotenoids, polyphenols, and essential fatty acids that possess potent antioxidant and anti-inflammatory properties. This study evaluated the effects of Cucurbita pepo seed oil on renal antioxidant biomarkers in the prophylaxis of Methotrexate-induced toxicity in male Wistar rats. Twenty-four male rats weighing between 150–200 g were randomly divided into four groups of six animals each. Group I served as the normal control and received distilled water. Group II received methotrexate to induce renal toxicity. Groups III and IV were pretreated with different doses of pumpkin seed oil prior to methotrexate administration. At the end of the experimental period, the animals were sacrificed and kidney tissues were harvested for biochemical analysis. Renal antioxidant biomarkers including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and malondialdehyde (MDA) were evaluated using standard biochemical methods. Results showed that methotrexate administration significantly increased lipid peroxidation as indicated by elevated MDA levels, while significantly reducing antioxidant enzyme activities (SOD, CAT, and GSH) compared with the control group. Pretreatment with pumpkin seed oil markedly improved the antioxidant status by significantly increasing SOD, CAT, and GSH levels and reducing MDA concentration in kidney tissues. The findings suggest that Cucurbita pepo seed oil possesses protective antioxidant properties capable of mitigating oxidative renal damage induced by Methotrexate. Therefore, pumpkin seed oil may serve as a potential natural prophylactic agent against drug-induced nephrotoxicity. Further studies are recommended to elucidate the precise mechanisms involved and to explore its potential therapeutic applications in clinical settings. Keywords: Renal oxidative stress, antioxidant biomarkers, pumpkin seed oil, methotrexate toxicity, nephroprotection, Wistar rats.