Molecular, Immunomodulatory, and Histopathological Role of Mesenchymal Stem Cells and Beetroot Extract on Cisplatin Induced Testicular Damage in Albino Rats

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Abstract
Cisplatin (Cis) a drug commonly used as a chemotherapeutic agent to treat various types of cancer, inducing testicular damage. The present study aimed to investigate the inhibitory potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and beetroot extract (BRE) in albino rats after testicular toxicity induced by cisplatin. Thirty adult male albino rats were grouped into: the control group, Cis group receiving a single dose of 7 mg/kg i.p. (intraperitoneal) to induce testicular toxicity, Cis plus BM-MSCs injected Cis followed by 2 × 106 of BM-MSCs; Cis plus BRE group receiving Cis followed by 300 mg/kg body weight/day of BRE, and Cis plus BM-MSCs and BRE group. In the current study, Cis reduced sperm count, serum testosterone level, and testicular activity of alkaline phosphatase (AKP), besides a marked inhibition of succinate dehydrogenase (SDH) activity. In addition, it significantly increased malondialdehyde (MDA) and along with a marked decrease in testis reduced glutathione content and total antioxidant capacity (TAC). At the same time, Cis administration resulted in a marked elevation in interleukine-6 and the iNOS and caspase-3 genes; however, it decreased the expression of steroidogenic acute regulatory protein (StAR). Combined treatment with BM-MSCs and BRE resulted in great improvement of all previous parameters. These results were also confirmed by histopathological and immunohistochemical examination. In conclusion, both MSCs and BRE were found to have potent potentials to inhibit testicular damage induced by cisplatin.

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