Abstract
Cisplatin (CP) is extensively used in the medical oncology field for malignancy treatment, but its use is associated with neurological side effects that compromise the patients' quality of life. Cytotherapy is a new treatment strategy for tissue damage that has recently emerged. The use of bone marrow-derived mesenchymal stem cells (BM-MSCs) was investigated for its therapeutic potential against CP-induced chemobrain as well as various models of brain damage. This study was carried out to elucidate, for the first time, the role of the intravenous injection (IV) of BM-MSCs against CP-induced neurotoxicity in a rat model through investigation of the parameters of oxidative stress, inflammation, and apoptosis in brain tissue. A rat model of neurotoxicity was generated by intraperitoneal injection of 7.5 mg/kg CP while 2 x 10(6) BM-MSCs was given by IV as a therapeutic dose. Injection of CP led to a significant rise in malondialdehyde and nitric oxide levels accompanied by a marked depletion of superoxide dismutase and reduced glutathione content in brain tissue in comparison to the normal control (NC) rats. Furthermore, a remarkable rise in the brain levels of inflammatory cytokines interleukin (IL)-1 beta and IL-6, together with the expression of apoptotic marker caspase-3, and the downregulation of the brain expression of proliferating marker Ki-67 in brain tissue were detected in the CP group compared to the NC group. Histopathological alterations were observed in the brain tissue of the CP group. BM-MSCs mitigated the biochemical and histopathological alterations induced by CP without affecting brain cell proliferation. BM-MSCs could be used as a promising neuroprotective agent against CP-induced neurotoxicity.