Erythropoietin Enhances Endogenous CD34+ Stem Cells Mobilization and Inhibits Caspase-3 Mediated Apoptosis in the Cardiac Muscle of Doxorubicin Treated Rats: Histological Study

Zidane, Noura Hassan; Hasanin, Nawal Awad; Sakkara, Zeinab Abd Elhay Abd Elhay; Hamed, Wafaa Saad; AbdElfattah, Amany AbdElfattah

doi:10.21608/ejh.2022.162368.1772

Erythropoietin Enhances Endogenous CD34+ Stem Cells Mobilization and Inhibits Caspase-3 Mediated Apoptosis in the Cardiac Muscle of Doxorubicin Treated Rats: Histological Study

Document Type : Original Article

Authors

¹ medical histology and cell biology faculty of medicine mansoura university

² medical histology and cell biology department, faculty of medicine, Mansoura University

³ medical histology and cell biology department faculty of Medicine Mansoura University

10.21608/ejh.2022.162368.1772

Abstract

Introduction: The use of Doxorubicin (DOX) as an antineoplastic drug is limited by its cardiotoxicity. Erythropoietin (EPO) has been suggested to be a powerful cardioprotective agent.
Aim of the Work: This study aimed to evaluate the protective role of EPO in DOX-induced cardiotoxicity and its role in mobilization of bone marrow-derived stem cells to the injured tissue.
Materials and methods: Thirty-two adult male albino rats (180-200 gm) were divided into equal four groups: control group (Gp I) received physiological saline (1 ml/kg/day), EPO group (Gp II) received recombinant human erythropoietin (rhEPO) (2500 IU/kg, 3 times a week), DOX-treated group (Gp III) received DOX (2.5 mg /kg, 3 times a week), DOX+EPO group (Gp IV) received DOX and rhEPO concomitantly. All medications were given by intraperitoneal injection for two weeks. Specimens from the left ventricles of all rats were prepared and stained for light microscopic study (hematoxylin & eosin, Masson’s trichrome and phospho-tungstic acid hematoxylin in addition to immunohistochemical staining for caspase-3 and CD34) and transmission electron microscopic study.
Results: DOX caused marked alteration in the histological features of the cardiac muscle fibers as well as a highly significant increase in area percentage of the collagenous fibers and caspase-3 immunoexpression. Co-administration of EPO with DOX caused improvement in the histological features of the cardiac muscle fibers, a highly significant decrease in area percentage of the collagenous fibers and caspase-3 immunoexpression, and a highly significant increase in CD34 immunoexpression.
Conclusion: EPO exerts cardioprotective effects on DOX-induced cardiomyopathy via anti-apoptotic and anti-fibrotic pathways as well as via mobilization of stem cells to the injured tissues.

Keywords