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Abstract
Background: Cisplatin is one of the most effective and potent anticancer drugs. It is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side effects such as nephrotoxicity. Bone marrow derived mesenchymal stem cells (MSCs) have shown great potential in cell therapy of solid organs. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. So we designed this work to evaluate the effect of MSCs and melatonin on cisplatin induced nephrotoxicity and to study the effect of melatonin on MSCs proliferation. Results: Histopathological examination of kidney tissue from rats which received cisplatin only, revealed the occurrence of nephrotoxicity. Administration of MSCs after induction of experimental nephrotoxicity slightly improved the histopathological picture with residual pathology while administration of melatonin, MSCs together with melatonin and MSCs pretreated with melatonin showed much more improvement of the histopathological picture specially the group of MSCs pretreated with melatonin. Gene expression in rat kidney tissue demonstrated that NFmB and caspase 3 were downregulated in all treated groups with more suppressive effect in the groups treated with MSCs together with melatonin and MSCs pretreated with melatonin specially the pretreated one. Beclin gene expression and Nrf2 protein levels were increased in all treated groups specially in the groups treated with MSCs together with melatonin and MSCs pretreated with melatonin. Serum levels of TNF Ü and MDA were decreased and those of IL-10 and GSH were increased in all treated groups specially the groups treated with MSCs together with melatonin and MSCs pretreated with melatonin. The melatonin treated MSCs showed significant increase in the proliferation rate and BCL2 gene expression and a significant decrease in BAX gene expression