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Modulation of Apoptosis and Oxidative Stress with Nesfatin-1 in Doxorubicin Induced Cardiotoxicity in Male Rat

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Abstract

Doxorubicin is a chemotherapy drug that can cause cardiotoxicity as an adverse side effect. Nesfatin-1 (Nesf-1) is a neuropeptide derived from nucleobindin2 in hypothalamus. In this study, due to its cardioprotective properties, the effect of Nesf-1 on doxorubicin induced cardiotoxicity was the aim for investigation. Forty mature male Wistar rats were randomly divided into four groups: Control, Nesf-1, cardiotoxicity (DOX) and DOX treated with nesf-1 (DOX + Nesf-1). Ejection fraction (%EF) and fractional shortening (%FS) were measured to evaluate cardiac function. In order to evaluate cardiac and liver injury (LDH, CK-MB, cTn-I, ALT, and AST) as well as oxidative stress markers (SOD, GSH, catalase, and MDA), ELISA assay was used. Immunohistochemical staining was utilized to evaluate apoptotic markers (Bax, Bcl-2 and caspase3). Myocardial fibrosis and histological changes were assessed via Masson’s trichrome and H&E staining, respectively. The results showed a significant improvement of cardiac functional parameters (percent of EF and FS), remarkable reduction of cardiac and liver injury markers (LDH, CK-MB, cTn-I, ALT and AST), cardiomyocytes apoptosis and percentage of cardiac fibrosis in DOX + Nesf-1 group in comparison to the DOX group. Moreover, less pathological changes and significantly reduced levels of MDA, catalase, and GSH levels were observed in DOX + Nesf-1 group compared to DOX group. Collectively, our findings demonstrate that Nesf-1 protects the heart from cardiotoxicity induced by DOX in rats by targeting apoptosis and oxidative stress. This study confirms validity of Nesf-1 to preserve structural integrity and also prevent myocardial dysfunction in patients who experience doxorubicin-induced cardiotoxicity.

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Acknowledgements

This study was financially supported by National Institute for Medical Research Development (NIMAD), Tehran, Iran. Grant No. 964414.

Funding

This study was financially supported by National Institute for Medical Research Development (NIMAD), Tehran, Iran. Grant No. 964414.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Kamran Rakhshan

  2. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran

    Fereshteh Dalouchi, Zeynab Sharifiaghdam, Atlasi Safaei & Fatemeh Jahanshahi

  3. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Yaser Azizi

  4. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Yaser Azizi

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  1. Kamran Rakhshan
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  2. Fereshteh Dalouchi
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  3. Zeynab Sharifiaghdam
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  4. Atlasi Safaei
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  5. Fatemeh Jahanshahi
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  6. Yaser Azizi
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Contributions

Conceptualization and Study design, YA; investigation and data collection, KR, FD, ZSH, and AS; writing—original draft preparation, KR, YA; writing—review and editing, KR, FJ and YA.

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Correspondence to Yaser Azizi.

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Rakhshan, K., Dalouchi, F., Sharifiaghdam, Z. et al. Modulation of Apoptosis and Oxidative Stress with Nesfatin-1 in Doxorubicin Induced Cardiotoxicity in Male Rat. Int J Pept Res Ther 28, 120 (2022). https://doi.org/10.1007/s10989-022-10429-7

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