Table of Contents
ISRN Pharmacology
Volume 2011, Article ID 430549, 8 pages
http://dx.doi.org/10.5402/2011/430549
Research Article

Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy

1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima Akiha-Ku, Niigata City 956-8603, Japan
2Department of Pharmacology, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia
3Department of Pharmacology, Faculty of Medicine and Health Sciences, Syarif Hidayatullah Jakarta, State Islamic University, South Jakarta 15412, Indonesia
4Department of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan

Received 31 January 2011; Accepted 10 March 2011

Academic Editors: M. Brunner and D. K. Miller

Copyright © 2011 Wawaimuli Arozal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Anthracyclines, most powerful anticancer agents, suffer from their cardiotoxic effects, which may be due to the induction of oxidative stress. Carvedilol, a third-generation, nonselective 𝛽 -adrenoreceptor antagonist, possesses both reactive oxygen species (ROS) scavenging and ROS suppressive effects. It showed protective effects against daunorubicin- (DNR-) induced cardiac toxicity by reducing oxidative stress and apoptosis. This study therefore was designed to examine the effects of carvedilol on DNR-induced cardiomyopathic rats, focused on the changes of left ventricular function, cardiac fibrosis, and hypertrophy. Carvedilol increased survival rate, prevented systolic and diastolic dysfunction, and attenuated myocardial fibrosis and hypertrophy. DNR alone treated rats showed upregulated myocardial expression of ANP, PKC- 𝛼 , OPN, and TGF- 𝛽 1 and downregulation of GATA-4 in comparison with control, and treatment with carvedilol significantly reversed these changes. The results of the present study add the available evidences on the cardioprotection by carvedilol when associated with anthracyclines and explain the mechanisms underlying the benefits of their coadministration.