Effect of allopurinol and benzbromarone on diabetic cardiomyopathy and vasculopathy in streptozotocininduced diabetic rats

Introduction: 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. Methods: 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. Results: 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. Conclusion: Allopurinol improved diabetic cardiomyopathy and aortic endothelial cell dysfunction in diabetic animals through antioxidant effects.