Protective Effects of Propranolol-Doxazosin Combination Against Dexamethasone-Induced Cardiotoxicity in Rats.

Background: Propranolol and doxazosin are well established and approved treatments of hypertension and cardiovascular disorders. According to our knowledge, the benefit of their combined use is not well investigated. Aim of the work: The present study explored the possible cardioprotective effect of propranolol-doxazosin combination against dexamethasone-induced cardiotoxicity. Material and methods: The study involved five experimental groups: control, dexamethasone (10 mg/kg subcutaneously), propranolol (30 mg/kg intraperitoneally), doxazosin (5 mg/kg intraperitoneally), and a combination of propranolol with doxazosin. Treatments were administered for seven days, before dexamethasone co-administered in the last four groups. The period of the administration was 7 days, then at 8th day, blood and heart samples were obtained. Levels of cardiac troponin I and the creatine kinase–myoglobin complex in serum were then analyzed as indicators of myocardial injury. Cardiac tissue samples were analyzed to determine the concentrations of diacylglycerol and malondialdehyde, as well as the kinase activity of Protein kinase B (Akt). Additionally, the expression levels of transforming growth factor-β (TGF-β), Smad3, and alpha-smooth muscle actin (α-SMA) were assessed. Histopathological and immunohistochemical examinations were also performed on cardiac samples to evaluate structural and molecular alterations. Results: The combined administration of propranolol with doxazosin significantly enhanced the cardio-protection against dexamethasone-induced cardiotoxicity conferred by either treatment alone. Conclusion: Propranolol-doxazosin combination is a promising treatment regimen against dexamethasone induced myocardial injury.