Adipose Tissue-Mesenchymal Stem Cells Improve Cisplatin-Induced Cardiotoxicity in Rats Via Modulating Apoptosis, Oxidative Stress, Inflammation, and Angiogenesis

Abstract

Background: Cardiotoxicity is a common adverse reaction to cisplatin treatment. Not all the mechanisms underlying cisplatin-induced cardiotoxicity have been described. Stem cells have been acknowledged as a potentially effective, novel treatment approach in treating several diseases. Objective: The current study was done to assess the impact of adipose mesenchymal stem cells (ADMSCs) in repairing cardiac damage induced by cisplatin and to investigate the underlying mechanisms.Materials and Methods: 32 rats were utilized for this study. They were randomly classified into four equal groups: the Control group that received saline intraperitoneally (i.p.), the Cisplatin-treated group that received a single i.p. injection of cisplatin at a dose of 7 mg/kg and was left for 5 days, Stem celltreated group that administered cisplatin as before and after 5 days they received a single dose of ADMSCs (1 × 10 6 ) mL injected intravenously and were left for 60 days after cell injection, and the Withdrawal group that received cisplatin in same dose and manner of administration as above and then left for 65 days. At the end of the experiment, the portions of the heart specimen were used to determine the levels of Total antioxidant capacity (TAC), cardiac Malondialdehyde (MDA), Tumur nuclear factor-α (TNF-α), and interleukin 2 (IL-2). The remaining portions of the heart muscle were prepared for histological and immunohistochemistry studies. Results: Cisplatin treated group revealed extensively disrupted organization of muscle fibers that appeared remarkably damaged with focal lysis with the widening of the spaces among the myofibrils, severely distorted nuclei which appeared highly condensed and had irregular malformed shapes with severe mitochondrial changes. Also, the levels of proinflammatory cytokines e.g., TNF-α and IL-2 were increased in the cardiac tissue. Also, increased MDA and decreased TAC levels were detected. Injection of ADMSCs ameliorated cardiotoxicity induced by cisplatin via suppression of oxidative injury, inhibition of pro-inflammatory cytokines, suppression of apoptotic cascades, and activation of angiogenesis. Conclusion: This study could be considered preliminary in proving that AD-MSCs therapy has a promising role to enhance marked regeneration of cisplatin-induced myocardial injury.