Indian Journal of Pharmacy and Pharmacology

Page: 229-234

Background: Hypertension is the leading cause of mortality for cardiovascular and renal diseases. Azilsartan medoxomil (AZL) available in fixed dose combination with chlorthalidone (CHL), is approved for patients with inadequate response to monotherapy with antihypertensives. Preclinical studies suggest pleiotropic effects of AZL. However, no studies have directly examined cardio-renal benefits of this combination. We investigated the effects of AZL/CHL combination on doxorubicin-induced cardiomyopathy and nephropathy in rats.

Aim & Objective: To induce cardiomyopathy and nephropathy in wistar rats by administering six equal intraperitoneal (I.p) injections (2.5 mg/kg) of doxorubicin over a period of 2 weeks (alternate days). and to investigate the effects of a combination of azilsartan medoxomil and chlorthalidone on doxorubicin induced cardiomyopathy and nephropathy in rats.

Materials and Methods: Doxorubicin (DOX) was administered to Wistar rats at a dose of 2.5mg/kg, i.p. in six injections for a period of two weeks. The effect of AZL 3mg/kg/d and its combination with CHL 2.5mg/kg/d, p.o. for 3 weeks, was studied on serum LDH, albumin, creatinine and lipid profile as well as myocardial and renal TBARS and GSH. The histology of cardiac and renal tissue was assessed by H.& E. staining. The combination was compared with that of AZL+Ramipril (RAM) 10mg/kg/d on DOX-induced cardiomyopathy and nephropathy.

Results: AZL/CHL and AZL/RAM significantly decreased the LDH, triglycerides, total & LDL cholesterol, creatinine and TBARS while increased the levels of albumin, HDL cholesterol, and GSH. DOX caused loss of myofibrils and vacuolization in the cardiac muscle, and hyaline casts with degenerative changes in the renal tubules. Whereas AZL/CHL revealed normal/less damaged myofibrils with no vacuolization, AZL/RAM revealed less damaged myofibrils with vacuolization. AZL/CHL showed normal glomerulus and tubular tissue while AZL/RAM revealed less damaged glomerulus and dilatation of tubular tissue.

Conclusion: The AZL/CHL combination was better than AZL/RAM and AZL alone in preventing doxorubicin-induced cardiomyopathy and nephropathy in rats.