Melatonin and zinc protect reproductive health in male rats during chemotherapy
Key takeaways
- Combining melatonin and zinc oxide nanoparticles significantly reduced reproductive damage in male rats, which was caused by the chemotherapy drug cyclophosphamide.
- The dual supplementation boosted testosterone levels and preserved sperm-producing cells more effectively than using either antioxidant alone.
- While the results show strong protection against oxidative stress in animal models, clinical trials are required to confirm if these benefits apply to humans.
A new rat model study suggests that supplementing with melatonin and zinc oxide nanoparticles may protect male reproductive health during chemotherapy with the drug cyclophosphamide. Scientists discovered that combining these antioxidants boosted testosterone production in rats, reduced oxidative stress, and preserved sperm-producing cells.
Zinc is essential for male reproductive function, and in nanoparticle form, the researchers say it can interact effectively with tissues to provide antioxidant protection. Meanwhile, they highlight melatonin as a “potent antioxidant,” neutralizing harmful free radicals and stimulating protective enzymes in cells.
“Our results show that cyclophosphamide causes clear harm to reproductive cells and hormones, mainly through oxidative stress,” comment the study 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.”
While commonly used to treat cancers and immune-related disorders, cyclophosphamide is known to damage rapidly dividing cells, including those in the testes, leading to reproductive toxicity.
Study parameters
The study authors note that the use of antioxidant supplements as a new therapeutic strategy to treat male infertility has attracted increasing attention. Their study published in Reproductive and Developmental Medicine involved 42 adult male rats divided into six groups.
One group received saline as a control, while another received cyclophosphamide alone. Two other groups received cyclophosphamide along with either melatonin or zinc oxide nanoparticles.
A fifth group received a triple combination of cyclophosphamide, melatonin, and zinc oxide nanoparticles. A final group received both melatonin and zinc oxide nanoparticles without chemotherapy.
All treatments were administered once a week for eight weeks. After this, researchers measured the rats’ reproductive hormones, oxidative stress markers, antioxidant enzyme activity, and the number of spermatogenic cells.
Synergistic benefits
The rats treated only with cyclophosphamide showed “substantial reproductive damage.”
For this group, testosterone and luteinizing hormone levels dropped sharply. Antioxidant enzyme activity decreased, oxidative stress marker levels increased, and the number of sperm-producing cells in the testes fell.
Melatonin and zinc oxide nanoparticles “partially improved” these damages on their own, but the most pronounced effects were observed when both compounds were used together, the study authors reveal.
Despite these implied benefits, they say clinical trials are needed to determine whether similar protective strategies could safely benefit men undergoing chemotherapy.
On World Cancer Day 2026, Danone strongly advocated that health practitioners recognize the role of nutritional care as an essential component of cancer treatment. It flagged that cancer-related malnutrition is a “prevalent yet overlooked challenge” in oncology, as up to 70% of people living with cancer experience malnutrition that hinders recovery.
