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Updated: Mar 20, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Obestatin attenuated doxorubicin-induced cardiomyopathy via enhancing long noncoding Mhrt RNA expression
Hong-Qi Li1, Yuan-Bo Wu2, Chang-Sen Yin1
1Department of Gerontology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Anhui Institute of Cardiovascular Disease, Hefei 230001, China.
Objective:
The emergence of side-effect of doxorubicin in cardiomyopathy and heart failure has led to the search for diverse strategies to prevent its cytotoxic effects. This study was to determine the role of obestatin on doxorubicin-induced cardiomyocytes apoptosis and possible underlying mechanism.
Methods:
Sprague Dawley rats were divided into 3 groups and received treatment for a total of 6 weeks: group1, untreated normal rats; group2, Doxorubicin-induced heart cardiomyopathy (DC) rats; and group3, obestatin treated HC rats. Doxorubicin (2.5mg/kg) or obestatin (100μg/kg/d) were discontinuously administered via intraperitoneal injection. Primary cardiomyocytes and H9C2 cell line were used for in vitro experiments. Mhrt and Nrf2 (nuclear factor erythroid 2 -related factor 2) mRNA expressions were determined using qRT-PCR. Expression of Nrf2 protein was determined using western blotting. TUNEL assay was performed to evaluate cell apoptosis.
Results:
Administration of obestatin significantly improved doxorubicin-induced dysfunction of left ventricular contractility function, moreover, resulted in upregulation of Mhrt and Nrf2 in failing myocardial tissue. Co-incubation of obestatin and doxorubicin in primary cardiomyocytes also enhanced Mhrt and Nrf2 expression as well as prevented cell apoptosis in comparison with doxorubicin only. Manipulation of cellular Mhrt by pcDNA-Mhrt or si-Mhrt transfection positively regulated Nrf2 expression in doxorubicin-incubated cardiomyocytes. Silencing Mhrt reversed cardioprotective effects of obestatin both in vivo and in vitro.
Conclusion:
Administration of obestatin attenuates doxorubicin-induced cardiac dysfunction via preservation of cardiomyocytes apoptosis in a Mhrt-Nrf2 dependent pathway.
Insights
Obestatin protects against doxorubicin-induced heart damage by preventing cell death. This effect is mediated through the Mhrt-Nrf2 pathway, preserving cardiac function.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Doxorubicin chemotherapy can cause cardiotoxicity, leading to heart failure.
- Identifying protective strategies against doxorubicin-induced cardiomyopathy is crucial.
Purpose of the Study:
- To investigate obestatin's role in preventing doxorubicin-induced cardiomyocyte apoptosis.
- To elucidate the underlying molecular mechanisms of obestatin's cardioprotective effects.
Main Methods:
- Animal model: Sprague Dawley rats treated with doxorubicin or obestatin for 6 weeks.
- In vitro studies: Primary cardiomyocytes and H9C2 cells exposed to obestatin and doxorubicin.
- Molecular analysis: qRT-PCR for Mhrt and Nrf2 mRNA, Western blotting for Nrf2 protein, TUNEL assay for apoptosis.
Main Results:
- Obestatin improved left ventricular contractility in doxorubicin-treated rats.
- Obestatin upregulated Mhrt and Nrf2 expression in cardiac tissue and cardiomyocytes.
- Obestatin prevented cardiomyocyte apoptosis, an effect dependent on Mhrt expression.
Conclusions:
- Obestatin attenuates doxorubicin-induced cardiac dysfunction by preserving cardiomyocytes.
- The cardioprotective mechanism involves a Mhrt-Nrf2 dependent pathway.
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