Publication Date:
2015-11-19
Description:
This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF- β ), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage ( -H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic ( β -MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α -MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of -H2AX + and 53BP1 + cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31 + , vWF + ) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit + and Sca-1 + cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1 + , CD90/53BP1 + , and r-H2AX + cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy.
Print ISSN:
0022-3565
Electronic ISSN:
1521-0103
Topics:
Medicine
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