Erythropoietin Enhances Endogenous CD34+ Stem Cells Mobilization and Inhibits Caspase-3 Mediated Apoptosis in the Cardiac Muscle of Doxorubicin Treated Rats: Histological Study | ||
| Egyptian Journal of Histology | ||
| Article 6, Volume 46, Issue 4, December 2023, Pages 1618-1636 PDF (39.87 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejh.2022.162368.1772 | ||
| Authors | ||
| Noura Hassan zidane* 1; Nawal Awad Hasanin2; Zeinab abd elhay Abd elhay Sakkara2; Wafaa Saad Hamed2; Amany AbdElfattah AbdElfattah3 | ||
| 1medical histology and cell biology faculty of medicine mansoura university | ||
| 2medical histology and cell biology department, faculty of medicine, Mansoura University | ||
| 3medical histology and cell biology department faculty of Medicine Mansoura University | ||
| 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 | ||
| Cardiotoxicity; caspase-3; CD34; doxorubicin; erythropoietin | ||
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