Spironolactone Attenuates Doxorubicin-induced Cardiotoxicity in Rats.

Abstract

In this study, we examined whether spironolactone (SP) could inhibit doxorubicin (DOX)-induced cardiotoxicity in the rat heart. 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. 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). This study show that SP may have a protective effect on DOX-induced cardiotoxicity.