Neuroprotective Effects of Melatonin on Neurotrophic, Apoptotic/Antiapoptotic and Inflammation Markers in the Rat Cerebrum and Cerebellum after Cranial Radiotherapy

This study aims to investigate the radioprotective effects of melatonin (MEL) against oxidative damage that may be caused by flattening filter (FF) and flattening filter-free (FFF) beam in the cerebrum and cerebellum of rat using various genetic markers. Forty female Wistar albino rats were randomly assigned to five groups. The control group received no intervention. The FF group received a single 16 Gy fraction at 600 MU/min. The FF+MEL group received the same FF protocol, preceded by melatonin (50 mg/kg, intraperitoneal) administered 15 min before irradiation. The FFF group received a single dose of 16 Gy at 2,400 MU/min. The FFF+MEL group received the same FFF protocol with melatonin administered as above. After treatment, cerebrum and cerebellum tissues were harvested, and mRNA expression levels of BDNF, CREB, BAX, BCL2 and IL6 were measured. Both FF and FFF radiotherapy treatments significantly increased BDNF, CREB, IL6, and BAX gene expression in cerebrum and cerebellum tissues, while decreasing BCL2 levels (P < 0.05). Melatonin treatment increased BDNF and CREB expression, significantly attenuated radiation-induced increases in IL6 and BAX, and partially reversed the decrease in BCL2 (P < 0.05). The increase in the BAX/BCL2 ratio after radiotherapy was significantly attenuated by melatonin treatment. Overall, FFF irradiation induced a stronger oxidative, inflammatory, and pro-apoptotic response than FF, whereas melatonin exhibited potent neuroprotective and anti-apoptotic effects. In conclusion, MEL demonstrates potential as a protective agent for healthy tissues during irradiations, owing to its antiapoptotic, anti-inflammatory, and neurotrophic properties.