effect of allopurinol and benzbromarone on diabetic cardiomyopathy and vasculopathy in streptozotocin-induced 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.