Abstract
Oxidative stress occurs in diabetic patients and experimental models of diabetes. The ability of l‐arginine to ameliorate the oxidative stress and metabolic changes after treatment with alloxan was investigated in rats. Adult male rats were injected intraperitoneally with 100 mg kg^−1^ of alloxan to produce experimental oxidative stress characteristic of diabetes mellitus. Hyperglycaemia and hypercholesterolaemia were observed in serum after 7 days of alloxan treatment. This was associated with a depression of glutathione (GSH) concentration as well as superoxide dismutase (SOD) and catalase (CAT) activities in the liver and brain. In addition, the thiobarbituric acid‐reactive substances (TBARS) were significantly elevated, indicating increased lipid peroxidation and oxidative stress in the same tissues. Administration of 100 mg kg^−1^ l‐arginine for 7 days either before or after alloxan injection significantly ameliorated the oxidative stress evidenced by a lower TBARS and a higher level of the endogenous GSH concentration and SOD and CAT activities than alloxan‐treated rats. These effects were paralleled by marked protection and partial prophylaxis against alloxan‐induced hyperglycaemia and cholesterolaemia. Thus, these results showed that exogenously administered l‐arginine might improve the clinical manifestation of diabetes mellitus and decrease the oxidative stress in the liver and brain. In addition, the study supports the beneficial effect of l‐arginine, which might be attributed to its direct, NO‐dependent antioxidant capacity and/or NO‐independent pathways. Copyright © 2004 John Wiley & Sons, Ltd.