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

SIMPLE SUMMARY: The chemotherapeutic agent Cisplatin (Cis) has testicular damage as a side effect. Therefore, efforts are being done by scientists to get over this effect. The current experiment was done to utilize bone marrow-derived stem cells (BM-MSCs) and beetroot extract (BRE) in reducing the Cis testicular damage in rats. In the current study, Cis reduced the sperm count, plasma testosterone level, the testicular activity of alkaline phosphatase beside a marked inhabitation of succinate dehydrogenase activity. Also, it significantly increased malondialdehyde and along with a marked decrease in testis reduced glutathione content and total antioxidant capacity. 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). Stem cell therapy (BM-MSCs) was accompanied with the use of herbal therapy (BRE) resulted in great improvement of all previous parameters. These results were confirmed by histopathological and immunohistochemical examination. In conclusion the current study recommends the use of beetroot as natural food in combination with stem cell therapy for the patient suffering from the testicular side effect of cisplatin chemotherapy. 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 × 10(6) 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.