Effect of allopurinol and benzbromarone on diabetic cardiomyopathy and vasculopathy in streptozotocin-induced diabetic rats

Allopurinol, a xanthine oxidase inhibitor, reduces both plasma uric acid (UA) and oxidative stress, and benzbromarone, a uricosuric agent, reduces the level of plasma UA. This study was designed to evaluate cardiac mechanical and endothelial functions of the allopurinol- and benzbromarone-treated diabetic rats, and to investigate the underlying mechanism (antioxidant or UA lowering activity) of allopurinol beneficial effects. Diabetes was induced by injecting streptozotocin to male Spargue-Dawley rats. Diabetic animals were treated with allopurinol and benzbromarone. After six weeks of treatment, left ventricular systolic/diastolic functions of hearts, contraction/relaxation responses to phenylephrine and acetylcholine of aortae, and serum levels of malondialdehyde, 8-isoprostane-2α and UA were measured. Diabetic cardiomyopathy and vasculopathy were characterized by reduced myocardial performance and decreased aortic endothelial response to the vasorelaxation effect of acetylcholine. The serum levels of malondialdehyde and 8-isoprostane-2α levels were elevated in diabetic animals. Allopurinol attenuated the diabetes-induced diastolic impairment of the hearts, endothelial dysfunction of the aortae and decreased oxidative stress parameters in serum; however, benzbromarone had none of these effects. Both, allopurinol and benzbromarone, diminished the elevated levels of UA in diabetic animals. Allopurinol improved diabetic cardiomyopathy and aortic endothelial cell dysfunction in diabetic animals through antioxidant effects.