Open AccessSpironolactone Attenuates Doxorubicin‐induced Cardiotoxicity in Rats
Author(s) -
Liu Guangzhong,
Liu Yongwu,
Wang Renjun,
Hou Tingting,
Chen Chaoyi,
Zheng Sijia,
Dong Zengxiang
Publication year - 2016
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/1755-5922.12189
Subject(s) - medicine , cardiotoxicity , spironolactone , doxorubicin , ejection fraction , cardiac function curve , apoptosis , cardiac fibrosis , heart failure , fibrosis , endocrinology , cardiology , pharmacology , chemotherapy , biology , biochemistry
Summary 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 QT c 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 ‐ β 1 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.