Radioprotective effect of a combination of melatonin and metformin on mice spermatogenesis: A histological study

Background: The spermatogenesis system includes highly radiosensitive cells. Hence, this system is a potential target for toxic effects of ionizing radiation during radiotherapy of abdomen and pelvis cancers, as well as after accidental radiation events. Accordingly, metformin and melatonin are two important radioprotectors that have shown an ability to prevent cell death through neutralization of free radicals and stimulating DNA damage responses.
Objective: To evaluate the radioprotective effects of melatonin and metformin on mice spermatogenesis when administered alone or as a combination.
Materials and Methods: In this histological Study, 40 (6-8 wk, 30 gr) NMRI mice were divided into 8 groups (n = 5/each) as control, metformin, melatonin, melatonin + metformin, radiation, radiation + melatonin, radiation + metformin, and radiation + melatonin + metformin. 37 days after the irradiation, the testicular tissues were collected for histological evaluation.
Results: Single administration of melatonin could ameliorate effectively radiation toxicity in mice testis. Metformin showed radioprotective effects on some parameters such as the numbers of spermatogonia and mature sperms. Interestingly, the melatonin and metformin combination reversed the reduced number of sperms rather than single drug administration.
Conclusion: The combination of melatonin with metformin can protect mice spermatogenesis against ionizing radiation more effectively compared to the single forms of these drugs.

Keywords
Radiation; Testis; Leydig cells; Melatonin; Metformin; Spermatogenesis.