L-Arginine ameliorates oxidative stress in alloxan-induced experimental diabetes mellitus.

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.