The role of spironolactone on myocardial oxidative stress in rat model of streptozotocin-induced diabetes

Abstract

Background: Diabetes mellitus (DM) is linked to cardiovascular diseases development and progression. Aldosterone contributes to cardiac oxidative stress and remodeling. Aim: To evaluate the impact of spironolactone (an aldosterone antagonist) on markers of myocardial redox status in a rat model of streptozotocin (STZ)-induced DM. Method: Adult Sprague Dawley rats were randomized into four groups; controls, spironolactone-treated rats (Spir), diabetic rats (DM), and diabetic rats treated with spironolactone (DM+Spir) for 4 weeks. Blood pressure and cardiac levels of aldosterone and oxidants/antioxidants were measured. Result: STZ-induced DM but did not cause hypertension or dyslipidemia in either spironolactone-treated or spironolactone-untreated rats. Aldosterone and aldosterone synthase levels were increased in both the DM and DM+Spir groups compared to control. In parallel, total nitrite and nitrotyrosine levels were increased and vitamin E antioxidant levels were reduced in the DM group. Spironolactone use reduced cardiac total nitrite levels and improved vitamin E levels. Glutathione reductase/peroxidase activities were increased in the DM and DM+Spir groups without changes in the ratio of reduced to oxidized form of glutathione. Superoxide dismutase (SOD) and catalase activities were increased in the DM group. Lipid peroxidation products were similar among the groups. Conclusions: The increase in total nitrite/nitrotyrosine in DM promoted significant compensatory increases in antioxidant activities of SOD, catalase and glutathione peroxidase/reductase probably to prevent cardiac oxidative damage. The use of spironolactone reduced nitrite generation and improved vitamin E levels independent of blood pressure.