Cardioprotective effects of ghrelin and Wharton’s jelly-derived mesenchymal stem cells, alone and in combination, in doxorubicin-induced myocardial injury in rats

Cardiovascular diseases represent one of the most serious health issues, accounting for worldwide morbidity and mortality. Doxorubicin (DOX) induces cardiotoxicity through the formation of free radicals. Stem cell therapy appears to be a promising alternative to existing treatments for myocardial injury, as it can produce growth factors and cytokines that are involved in wound healing. Besides its orexigenic properties, ghrelin was proven to have a cardiovascular protective effect. The present study was designed to compare the possible protective role of ghrelin to Wharton jelly-derived mesenchymal stem cells (WJ-MSCs) as well as their combined effect in doxorubicin-induced cardiotoxicity in rats. Forty adult male albino rats were divided into five groups: Group (I): normal control group, Group (II): DOX induced cardiotoxicity group, Group (III): ghrelin treated group, Group (IV): MSCs treated group and Group (V): ghrelin and MSCs (combined) treated group. Cardiac enzymes, oxidative stress markers, apoptotic markers in cardiac tissue and cardiac performance parameters using Langendorff apparatus and echocardiography, were assessed. At the end of the experiment, histopathological evaluation of the injured myocardium was conducted using hematoxylin and eosin (H&E), Masson’s trichrome staining, and immunohistochemical analysis for nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Our results revealed a significant amelioration of the aforementioned parameters almost towards normal values in the three treatment groups. Histopathological examination and immunohistochemical assessment of Nrf2 & HO-1 revealed improvement in the three treated groups, particularly those receiving stem cell therapy.