International Journal of Radiation Biology, 2026 (SCI-Expanded, Scopus)
Purpose: This study investigated the radioprotective effect of melatonin (Mel) on small intestinal damage in healthy rats exposed to Flattening Filter (FF) and Flattening Filter Free (FFF) X-rays during radiotherapy, with a comparative evaluation of the biological effects of FF and FFF irradiation on intestinal tissue injury. Materials and methods: Forty male Sprague-Dawley rats (12 weeks, 250±20 g) were randomly assigned to five groups. Group 1 (Control) received no treatment. Group 2 (FF) was exposed to 8 Gy radiotherapy at 4 Gy/min to the abdominopelvic region. Group 3 (FF+Mel) received melatonin 15 minutes before the same irradiation. Group 4 (FFF) was treated with 8 Gy at 14 Gy/min, and Group 5 (FFF+Mel) received melatonin before this exposure. Intestinal tissues were collected 48 h after the experimental procedures and evaluated histopathologically using hematoxylin–eosin (H&E) and periodic acid–Schiff (PAS) staining, immunofluorescently by 8-hydroxy-2′-deoxyguanosine (8-OHdG) antibody labeling, and biochemically by measuring serum 8-OHdG and malondialdehyde (MDA) levels. Results: Significant histopathological differences were observed between the control (G1) and irradiated groups (FF (G2); FFF (G4)), including mucosal disruption, crypt loss/dilatation, goblet cell reduction, and hemorrhage. In addition, 8-OHdG expression was significantly higher in the FFF group (G4) compared to the FFF+Mel group (G5) (p<0.05). Biochemically, both 8-OHdG and MDA levels were elevated in irradiated groups (G2, G4) compared with controls (p<0.05). Notably, melatonin administration significantly reduced oxidative stress markers, with differences between FF (G2) and FF+Mel (G3), as well as FFF+Mel (G5) (p<0.05). Conclusion: Melatonin significantly reduced radiotherapy-induced oxidative stress and apoptosis in healthy small intestinal tissue histopathologically and biochemically. These findings suggest that melatonin may act as an effective radioprotective agent by preserving small intestinal integrity during abdominopelvic radiotherapy.