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



Rakhshan K¹ ; Dalouchi F² ; Sharifiaghdam Z² ; Safaei A² ; Jahanshahi F² ; Azizi Y^{3, 4}
Source: International Journal of Peptide Research and Therapeutics Published:2022

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. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.