This study was designed to investigate the protective effects of vitamin C and vitamin A on oxidative renal tissue damage. Male Wistar rats were given an intraperitoneal injection of 0.5 ml saline (control) or 0.5 ml solution of lipopolysaccharide (10 mg/kg), which caused endotoxemia. Immediately (within 5 min) after the endotoxin injection, the endotoxemic rats were untreated or treated with intraperitoneal injection of vitamin A (195 mg/kg bw), vitamin C (500 mg/kg bw) or their combination. After 24 hours, tissue and blood samples were obtained for histopathological and biochemical investigation. Endotoxin injection caused renal tissue damage and increased erythrocyte and tissue malondialdehyde (MDA) and serum nitric oxide (NO), urea and creatinine concentrations, but decreased the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared to the parameters of control animals. Treatment with vitamin C or with vitamins C and A significantly decreased the MDA levels and serum NO, urea and creatinine levels, recovered the antioxidant enzyme activities (SOD, GSH-Px and CAT), and prevented the renal tissue damage in endotoxemic rats. In contrast, vitamin A alone did not change the altered parameters except for creatinine levels. Notably, the better effects were observed when vitamins A and C given together. It is concluded that vitamin C treatment, alone or its combination with vitamin A, may be beneficial in preventing endotoxin-induced oxidative renal tissue damage and shows potential for clinical use. - endotoxemia; vitamin A; vitamin C; malondialdehyde; kidney (c) 2005 Tohoku University Medical Press.