Spironolactone Attenuates Doxorubicin-induced Cardiotoxicity in Rats

Abstract

Introduction: In this study, we examined whether spironolactone (SP) could inhibit doxorubicin (DOX)-induced cardiotoxicity in the rat heart. Methods: Rats were randomized into four groups (n = 6): (1) the control group; (2) the SP group; (3) the DOX group; and (4) the SP + DOX group. The rats were evaluated for electrocardiography and cardiac function. The cardiac collagen, cardiomyocyte apoptosis, and the remodeling-related proteins were determined. Results: Rats treated with DOX showed prolongation of QTc and decreased left ventricular ejection fraction (EF) and fractional shortening (FS) (P < 0.05) showed left ventricular end-diastolic dimensions (LVEDD) and left ventricular end-systolic dimensions (LVESD) were significantly increased (P < 0.05). SP prevented these pathophysiological alterations (P < 0.05). In DOX-treated group, cardiac fibrosis, apoptotic cell number, and cardiac collagen volume fraction were higher than control group (P < 0.05); these effects were prevented by cotreatment of SP (P < 0.05). Moreover, the expressions of TGF-β1 and phosphorylated-Smad3 were increased after DOX treatment (P < 0.05) and significantly reduced by coadministration of SP (P < 0.05). Conclusions: This study show that SP may have a protective effect on DOX-induced cardiotoxicity.