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Recent studies have suggested a potential direct role of mild hyperuricemia in development of chronic kidney disease independent of urate crystal formation. The present study was designed to investigate the possible anti-hyperuricemic and renoprotective effect of vitamin C, as a natural antioxidant with uricosuric property on a rat model with chronic mild hyperuricemia-induced nephropathy. A model of mild hyperuricemia was induced in male Wistar rats with an uricase inhibitor, oxonic acid (OA) (750 mg/kg per day for 4 weeks by gastric gavage). Rats were divided into four groups: (1) control; (2) OA only; (3) OA + vitamin C (200 mg/kg for 4 weeks by gastric gavage); and (4) vitamin C only. At the end of the study, rats were sacrificed under diethyl ether general anesthesia and serum levels of uric acid, creatinine and blood nitrogen urea (BUN) as well as glutathione (GSH) levels and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were measured as indices of oxidative stress and anti-oxidative status in kidney tissues. Also, histopathological examination of isolated kidney tissues was performed. The administration of OA resulted in 2.4 fold increase in serum uric acid levels, and was associated with development of kidney damage characterized by a significant increase in serum levels of creatinine and BUN, and significant decreases in renal GSH levels and activities of SOD, GPx and GST.By contrast, simultaneous administration of vitamin C significantly ameliorated all these biochemical changes induced by OA. The histopathological findings supported these biochemical observations …