Premature ovarian failure (POF) is described as a loss of oocytes and the absence of folliculogenesis and is considered an adverse effect of chemotherapeutic drugs, which leads to infertility. Subsequently, the existing inquiry was achieved by exploring the potential suspicious influences of lemon peel extract (LPE), and resveratrol (RES) on cyclophosphamide (CPA) induced-POF. The results showed that CPA-induced POF significantly decreased serum estradiol (E2) and progesterone levels, along with a considerable rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Moreover, CPA administration to rats significantly increased the serum level of Malondialdehyde (MDA) and significantly lowered the levels of reduced glutathione (GSH) and superoxide dismutase (SOD); in addition, it increased nuclear factor kappa B (NF-κB) levels, tumor necrosis factor-α (TNF-α), as well as cyclooxygenase 2 (COX-2) with the spread expression of inducible nitric oxide synthase (iNOS) mRNA levels and caspase-3 (Casp3) levels in ovarian tissues versus the control rats. However, treatment with LPE and RES suppressed the triggering of NF- κB pathways, evidenced by a considerable reduction in Casp3 & iNOS mRNA expression level and significant ameliorative effects in all evaluated parameters, as confirmed by the histological and immunohistochemical investigation when comparing the model group. In overall findings, both lemon peel extract and resveratrol can mitigate the adverse effects of CPA-induced POF. Most crucially, its combination therapy is a promising pharmacological agent for this disease.

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.

The present study was established to investigate the role of bone marrow mesenchymal stem cells (MSCs) and melatonin (MT), alone or in combination with each other for improvement of beta cell functions in STZ-induced diabetic rat model. Also, to evaluate the role of melatonin in increasing the efficacy of MSCs. Fifty two male albino rats (130-150g) were divided into six groups. Control: received phosphate buffer saline PBS; Melatonin group received melatonin (10 mg/kg b.wt. day for 2 months by oral intubation); Diabetic untreated group; Diabetic group treated with melatonin; Diabetic group treated with mesenchymal stem cells (MSCs) (A single intravenous injection of 3×106 cell in PBS )and Diabetic group treated with both stem cells and melatonin. Diabetes was induced by a single i.p. injection of 45mg/kg b.wt. of streptozotocin. The results showed that treatment of diabetic rats with either MSCs alone or in combination with melatonin resulted in an increase in body weight and pancreas weight. The biochemical analysis showed significant improvement in glucose, insulin, total antioxidant and malondialdehyde level in diabetic rats treated with either MSCs alone or in combination with melatonin. On the other hand, the results of imumuno-histochemical analysis showed that MSCs and/or melatonin treatment reduced the rate of inflammation and apoptosis of the Islet cells of pancreases as well as increased the rate of pancreatic cell division. Such results were indicated by a significant improvement in the level of TNF-α, IL-10, PCNA, and caspase-3 to levels very close to the control. The microscopic examination of Langerhans islands showed that treatment with MSCs either alone or in combination with melatonin resulted in an improvement in the tissue of the pancreas and reduced number of damaged beta cells. It can be concluded that stem cell therapy has a significant role in restoring the structural and functional efficiency of beta cells in the pancreas. The results also showed that co- treatment of stem cells and melatonin was more effective than stem cell alone. Such result may be due to the role of melatonin as an antioxidant in increasing the efficiency and vitality of stem cells.