Prevention of Adriamycin induced cardiotoxicity in rats — A comparative study with subacute angiotensin-converting enzyme inhibitor and nonselective beta blocker therapy

Abstract

Back groundCardiotoxicity confines the usage of Adriamycin in clinical practice as it can develop cardiac impediments up to 10years after the termination of therapy. Even though, no specific therapeutic strategies are available for treating adriamycin-induced cardiotoxicity, beta-adrenergic blockers (βB) and angiotensin-converting enzyme (ACE) inhibitors are known to prevent its progression into failure. In this scenario, we attempted to compare the pharmacological outcome of sub-acute βB and ACE inhibitor treatments in preventing adriamycin-induced cardiotoxicity by analysing the differences between them. MethodsRats received a single bolus dose of adriamycin (10mg/kg) on day one and treated with either Carvedilol (10mg/kg) (CAR) or Captopril (50mg/kg) (CAP) once daily for 28days. Cardiac morphology, systolic and diastolic functions were evaluated by 2D trans-thoracic echocardiography. Cardiac Troponin and Ck MB levels were measured to analyse the myocyte damage. Myocardial lipid peroxidation, IL1β levels and caspase 3 activity were evaluated as the markers of oxidative stress, inflammation and apoptosis respectively. ResultsBoth treatments had reduced the adriamycin induced cardiotoxicity. Whereas CAP treatment showed a better reduction of inflammation, superior preservation of posterior wall architecture and enhanced improvement in relative wall thickness when compared to CAR. Oxidative stress, caspase 3 activity and markers of myocyte damage were better recovered with CAR treatment while other parameters were found to be identically attenuated. ConclusionThe present study found an identical therapeutic outcome from ACE inhibition and β blockade with a better attenuation of inflammation and structural preservation with ACE inhibition and superior antioxidant and antiapoptotic effect with βB treatment.