This study tested for benefits of early administration of carvedilol against doxorubicin-induced cardiomyopathy. After 35 days, the left-ventricular ejection fraction (LEVF) was significantly lower in the group administered doxorubicin without carvedilol compared to animals administered carvedilol along with the doxorubicin. The protein expressions of fibrotic (Smad3, TGF-β), apoptotic (BAX, cleaved caspase 3, PARP), DNA-damage (γ-H2AX), oxidative-stress (oxidized protein), mitochondrial-damage (cytosolic cytochrome-C), heart failure (BNP), hypertrophic (β-MHC) biomarkers of LV myocardium showed higher levels in the animals not treated with carvedilol. The protein expressions of anti-fibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt were increased in animals treated with only doxorubicin. Interestingly, in the present study doxorubicin-induced cardiotoxicity enhanced the generation of cardiac stem cells in myocardium. Of importance was that carvedilol therapy further enhanced this phenomenon of progenitor cell renewal.
See article at J Pharmacol Exp Ther 2015 355:516-525.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics