L-arginine administration exacerbates myocardial injury in diabetics via prooxidant and proinflammatory mechanisms along with myocardial structural disruption

BACKGROUND L-arginine (L-Arg) is one of the most widely used amino acids in dietary and pharmacological products. However, the evidence on its usefulness and dose limitations, especially in diabetics is still controversial. AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats METHODS Of 96 male rats were divided into 8 groups as follows (n = 12): Control, 0.5 g/kg L-Arg, 1 g/kg L-Arg, 1.5 g/kg L-Arg, diabetic, diabetic + 0.5 g/kg L-Arg, diabetic + 1 g/kg L-Arg, and diabetic + 1.5 g/kg L-Arg; whereas L-Arg was orally administered for 3 months to all treated groups. RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats, but when given to diabetics a significant upregulation was observed, associated with increased nitric oxide, inflammatory cytokines, and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg. A substantial decrease in the antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione concentrations, and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups, associated with myocardial injury, fibrosis, α-smooth muscle actin upregulation, and disruption of desmin cardiac myofilaments, and these effects were not noticeable at normal treated groups. On the other hand, L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights. CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium, while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.