PROPHYLACTIC AND THERAPEUTIC POTENTIAL EFFECTS OF MELATONIN PRETREATED BONE MARROW MESENCHYMAL STEM CELLS AGAINST CISPLATIN-INDUCED CARDIAC TOXICITY IN ALBINO RATS
Ahmed W. Elzainy
Anatomy and Embryology, Faculty of Medicine, Cairo University, Qassim University
Introduction: Cisplatin, one of the most effective chemotherapeutic agent, is proved to have toxic effects on many body organs especially the heart. Bone marrow mesenchymal stem cells (BM-MSCs) and melatonin were investigated to treat myocardial toxicity separately. However, their concomitant potential effect was not properly investigated. Aim of the work: The present study was conducted to evaluate the potential prophylactic and therapeutic effects of BM-MSCs pretreated with melatonin against cisplatin myocardial toxicity. Material and Methods: Twenty adult male albino rats were divided into four groups; group I (control group), did not receive any drugs, group II (given 10 mg/kg body weight Cisplatin in a single dose) and group III and IV (given the same dose of cisplatin and one systemic injection of melatonin pretreated BM-MSCs (1 x 106) diluted in 0.5 ml of PBS at day one (group III) as a prophylactic treatment and at day 14 (group IV) as a therapeutic dose. Blood samples were analyzed for serum cardiac marker enzymes; CK-MB and troponin 1. Samples from the left ventricle were taken and prepared for fluorescent study, gene expression for TNF-α, IL-1ß and NF-ҡß levels, light microscopic examination, α-SMA and Bax immunohistochemical study and histomorphometric analysis. Results: The present study confirmed the myocardial toxic effect of cisplatin, manifested by significant increase in serum CK-MB and troponin 1 and in the expression of pro-inflammatory factors; TNF-α, IL-1ß and NF-ҡß levels. Degeneration of myocardial cells and nuclear pyknosis with congested blood vessels and blood extravasation were detected. Significant increase in α SMA and increase in Bax immunoreaction were revealed. Melatonin pretreated BM-MSCs were shown to protect and regenerate the cardiomyocytes. Prophylactic treated group showed significantly better effects than therapeutic group. Conclusion: The present study confirmed that prophylactic treatment is more efficient than therapeutic treatment of melatonin pretreated BM-MSCs against the cardiac toxicity of cisplatin. So, it is recommended to begin with them from the start in concomitant with cisplatin chemotherapy.