Spironolactone Attenuates Doxorubicin-induced Cardiotoxicity in Rats.
BACKGROUND
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.
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Guangzhong
G
Liu
Heihongjiang University of Chinese Medicine, Harbin, China.
Yongwu
Y
Liu
Department of Biotechnology, School of Life Science, Jilin Normal University, Siping, China.
Renjun
R
Wang
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Tingting
T
Hou
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Chaoyi
C
Chen
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Sijia
S
Zheng
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Zengxiang
Z
Dong
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066126:Cardiotoxicity / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004317:Doxorubicin; D005355:Fibrosis; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D002316:Cardiotonic Agents; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D013148:Spironolactone; D004317:Doxorubicin; D003094:Collagen
Cardiotoxicity; Doxorubicin; Smad3; Spironolactone; TGF-β1