Effect of melatonin and zinc oxide nanoparticles against oxidative stress and male reproductive toxicity induced by cyclophosphamide

Objective: Cyclophosphamide (CP) is an anticancer drug that induces oxidative stress, leading to gonadal toxicity. This study aimed to evaluate the effectiveness of co-treatment with zinc oxide nanoparticles (nZno) and melatonin (Mel) on lipid peroxidation and antioxidant enzyme levels against CP-induced testicular damage. Methods: In this study, 42 adult male rats were divided into six groups. The control group received intraperitoneal (i.p.) saline solution. The CP group was administered CP at 60 mg/kg/week. The Mel + CP and nZno + CP groups received CP along with 10 mg/kg Mel and 5 mg/kg nZno, respectively. The Mel + nZno + CP group received CP plus 10 mg/kg Mel and 5 mg/kg nZno, simultaneously. The Mel + nZno group received 10 mg/kg Mel and 5 mg/kg nZno simultaneously. Eight weeks after the treatment, hormonal assays, total antioxidant capacity (TAC), histological studies, lipid peroxidation levels, and antioxidant enzyme status were assessed. Results: Biochemical results showed that CP decreased spermatogenic lineage cells, TAC, levels of antioxidant enzymes catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px), and reproductive hormone levels luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone, and increased malondialdehyde (MDA) content. In contrast, co-treatment with Mel and nZno in the Mel + nZno + CP group resulted in a significant improvement in all examined parameters ( P < 0.05). Conclusion: The results indicate that the simultaneous administration of Mel and nZno could be used as a potential protective agent against CP-induced reproductive toxicity.