article · Pharmaceuticals
Abdelmonem Awad HegazyCyclophosphamide is an antiproliferative and cytotoxic drug that causes toxic effects on male fertility. This research examined whether hesperidin could alleviate cyclophosphamide-induced testicular damage in male albino rats. Cyclophosphamide significantly reduced levels of key hormones, including testosterone, luteinising hormone, follicle-stimulating hormone, and prolactin, while impairing testicular antioxidant capacity. It also increased markers associated with oxidative stress, inflammation, and cell death, while downregulating critical genes in the hypothalamic-pituitary-gonadal axis and steroidogenesis pathways. Administering hesperidin alongside cyclophosphamide reversed many of these adverse effects. The combination improved reproductive hormone levels, enhanced antioxidant defences, and reduced inflammatory and apoptotic markers. These outcomes suggest that hesperidin can counter cyclophosphamide-induced reproductive toxicity by modulating hormonal regulation, steroidogenesis, inflammation, and cellular survival.
Cyclophosphamide is a common chemotherapy agent whose clinical utility is often limited by severe reproductive toxicity leading to male infertility. Understanding how hesperidin protects testicular function, restores hormonal balance, and reduces cellular inflammation offers a biological basis for developing protective interventions that preserve fertility in patients undergoing cytotoxic drug treatments.
The research points towards hesperidin as a potential supportive adjuvant for pharmaceutical or nutraceutical formulations targeting chemotherapy-induced reproductive toxicity. Potential beneficiaries include oncologists, fertility specialists, and pharmaceutical developers focused on male fertility preservation. As this work is early-stage animal research, further preclinical toxicology, formulation optimisation, and human clinical trials are required before any therapeutic product can be developed or commercialised.
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Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA), and p53, and iNOS immune expression, compared to the control group. A significant downregulation in hypothalamic KISS-1, KISS-1r, and GnRH, hypophyseal GnRHr, and testicular mRNA expression of steroidogenesis enzymes, PGC-1α, PPAR-1, IL10, and GLP-1, as well as a significant upregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP-treated group in comparison to that in the control group. The administration of HSP in CP-treated rats significantly improved the levels of serum LH, FSH, testosterone, prolactin, testicular GPx, and TAC, with a reduction in levels of MDA, and p53, and iNOS immune expression compared to the CP-treated group. A significant upregulation in hypophyseal GnRHr, and testicular mRNA expression of CYP19A1 enzymes, PPAR-1, IL10, and GLP-1, as well as a significant downregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP+HSP-treated group in comparison to that in the CP-treated group. In conclusion, HSP could be a potential auxiliary agent for protection from the development of male infertility.
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DOI: 10.3390/ph16020301
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