A recent study in Reproductive and Developmental Medicine shows that combining melatonin with zinc oxide nanoparticles can protect male reproductive health in rats treated with the chemotherapy drug cyclophosphamide . The research found that the combination of these antioxidants improved hormone levels, reduced oxidative stress, and preserved sperm-producing cells in the testes.
Cyclophosphamide is commonly used to treat cancers and immune-related disorders, but it is known to damage rapidly dividing cells, including those in the testes, leading to reproductive toxicity. The study aimed to test whether melatonin, zinc oxide nanoparticles, or both could reduce these harmful effects by counteracting oxidative stress.
In the study, 42 adult male rats were divided into six groups. One group served as a control, one received cyclophosphamide alone, and other groups received cyclophosphamide together with melatonin, zinc oxide nanoparticles, or both. A final group received melatonin and zinc oxide nanoparticles without chemotherapy. All treatments were administered once a week for eight weeks. Researchers then measured reproductive hormones, oxidative stress markers, antioxidant enzyme activity, and the number of spermatogenic cells in the testes.
Rats treated with cyclophosphamide alone showed substantial reproductive damage. Testosterone and luteinizing hormone levels dropped sharply, antioxidant enzyme activity decreased, oxidative stress marker levels increased, and the number of sperm-producing cells fell. Melatonin or zinc oxide nanoparticles alone partially improved these damages, but the most pronounced effects were observed when both compounds were used together.
“Our results show that cyclophosphamide caused clear harm to reproductive cells and hormones, mainly through oxidative stress,” said authors from the Mazandaran University of Medical Sciences, Iran. “But when melatonin and nano-zinc oxide were given together, many of these harmful changes were significantly reduced.”
The study explains that melatonin acts as a potent antioxidant, neutralizing harmful free radicals and stimulating protective enzymes in cells, while also supporting testosterone production and sperm maturation. Zinc is essential for male reproductive function, and in nanoparticle form, it can interact effectively with tissues to provide antioxidant protection. Despite these functions, clinical trials will be needed to determine whether similar protective strategies could safely benefit men undergoing chemotherapy. For now, the findings add to growing evidence that antioxidant-based approaches may play a role in protecting male reproductive health during cancer treatment.
Reproductive and Developmental Medicine
Experimental study
Effect of melatonin and zinc oxide nanoparticles against oxidative stress and male reproductive toxicity induced by cyclophosphamide
11-Aug-2025