Abstract
BackgroundThe therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) against cisplatin-induced nephrotoxicity has been reported, however, its efficacy in gonadotoxicity still has not been addressed. Herein, we investigated the effect of BM-MSCs in cisplatin-induced testicular toxicity and its underlying mechanism of action.MethodsThirty male Sprague–Dawley rats were divided into a control group: injected with phosphate-buffered saline (PBS) intraperitoneal (ip), a cisplatin group: injected with a single dose of 7 mg/kg cisplatin ip to induce gonadotoxicity and a BM-MSCs group: received cisplatin ip followed by BM-MSCs injection 1 day after cisplatin. In testicular tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were assessed. Additionally, gene expressions of inducible nitric oxide synthase (iNOS), caspase-3, and p38 mitogen-activated protein kinase (MAPK) were measured. The testicular tumor necrosis factor alpha (TNF-α) protein contents and Bcl-2 associated X protein (BAX) expression were determined. Histopathology of testicular tissues was examined.ResultsCisplatin injection showed a significant decrease in GSH and SOD testicular levels besides a significant increase of MDA and TNF-α testicular levels and upregulation of testicular gene expressions of iNOS, caspase-3, and p38-MAPK in comparison to the control group. Moreover, a marked increase in BAX protein expression was observed in the cisplatin group when compared with the control one. Histopathological examination exhibited significant seminiferous tubules atrophy in cisplatin-treated rats.ConclusionsThe BM-MSCs injection significantly repaired the testicular injury and improved both biochemical and histopathological changes. The MSCs mitigated the gonadotoxicity induced by cisplatin through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.
Highlights
The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-Mesenchymal stem cells (MSC)) against cisplatin-induced nephrotoxicity has been reported, its efficacy in gonadotoxicity still has not been addressed
Characterization and transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) The MSCs were identified by their morphology, adherence, surface markers, and their capacity to differentiate into osteocytes and adipocytes as detected by an inverted microscope (Leica, Wetzlar, Germany)
Cell surface antigen expression of BM-MSCs was analyzed by flow cytometry in which cells were incubated with fluorescein isothiocyanate-conjugated or phycoerythrincyanine-5-conjugated or rat immunoglobulin G (IgG) isotype control antibodies for 30 min at 4 °C in phosphate-buffered saline (PBS) [20]
Summary
The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) against cisplatin-induced nephrotoxicity has been reported, its efficacy in gonadotoxicity still has not been addressed. Mesenchymal stem cells (MSCs) are kind of multipotent stem cells isolated from many tissues like bone marrow, adipose tissue, cord blood, and amniotic membrane [9]. They are characterized by specific surface antigen expression in addition to osteogenic, chondrogenic, and adipogenic differentiation; they have the ability to self-renew [7, 10, 11]. It was documented that bone marrow-derived mesenchymal stem cells (BM-MSCs)
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