Startseite Medizin Effect of ghrelin on VEGF-B and connexin-43 in a rat model of doxorubicin-induced cardiomyopathy
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Effect of ghrelin on VEGF-B and connexin-43 in a rat model of doxorubicin-induced cardiomyopathy

  • Mona G. Elhadidy , Ahlam Elmasry EMAIL logo , Mohammed R. Rabei und Ahmed E. Eladel
Veröffentlicht/Copyright: 14. November 2019

Abstract

Background

Since their discovery in the early 1960s, doxorubicin (DOX) remains the most effective anticancer drug. However, this drug has confirmed to be a double-edged sword because it causes a cardiomyopathy that leads to congestive heart failure. Ghrelin, a multi-functional peptide, plays an important role in cardiovascular protection. Therefore, we investigated the effects of ghrelin on vascular endothelial growth factor-beta (VEGF-B) and connexin-43 (Cx43) expression in DOX-induced cardiomyopathy.

Methods

Forty adult male rats were divided randomly into four groups: normal, normal + ghrelin, DOX-induced cardiomyopathy, and DOX-induced cardiomyopathy + ghrelin. Biochemical and histopathological analysis, electrocardiograph (ECG), heart rate, systolic blood pressure (SBP), and immunohistochemical staining of VEGF-B and Cx43 were assessed for all rats in heart tissue specimens. The duration of the study was 2 weeks.

Results

DOX-induced cardiomyopathy in rats showed significant ECG changes such as prolongation of PR, QT, QTC intervals and ST segment, a decrease in amplitude and an increase in the duration of QRS complex, bradycardia, and a decrease in SBP. Also, rats in the DOX group showed myocardial histopathological damage in the form of severe fibrosis with decreased expression of Cx43 and a non-significant difference in expression of VEGF-B when compared to normal rats. Treatment with ghrelin resulted in a significant improvement in all the studied parameters and was associated with an increase in VEGF-B and Cx43 expression.

Conclusions

Ghrelin has a beneficial effect against DOX-induced cardiomyopathy which may be mediated through VEGF-B and Cx43 expression in the myocardium. Ghrelin is a promising cardioprotective drug in DOX-induced cardiomyopathy patients, but further studies are needed to evaluate its use.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors state no conflict of interest.

  4. Ethical approval: The protocol of this work (code number: R.18.09.264) was approved by the Ethical Committee of the institutional research board, Mansoura Faculty of Medicine, Egypt, which is complied with the World Medical Association Declaration of Helsinki.

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Received: 2018-12-07
Accepted: 2019-09-28
Published Online: 2019-11-14

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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