Dose-rate–dependent radioprotective effects of melatonin on gastric tissue under FF and FFF radiotherapy: Modulation of 8-OHdG and cytokine-mediated oxidative and inflammatory responses
Tissue and Cell, cilt.101, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 101
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.tice.2026.103486
- Dergi Adı: Tissue and Cell
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Zoological Record
- Anahtar Kelimeler: Gastric tissue, Melatonin, Oxidative stress, Radiotherapy-induced, Pro & anti-inflammatory cytokine, 8-OHDG, 8-OHDG
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Purpose: Radiotherapy of abdominal and thoracic malignancies often results in unintended exposure of healthy gastrointestinal tissues, leading to oxidative stress, inflammation, and DNA damage in the gastric mucosa. Melatonin, a potent endogenous antioxidant with well-established anti-inflammatory and free radical–scavenging properties, has been proposed as a promising radioprotective agent. This study aimed to investigate the dose-rate–dependent radioprotective effects of melatonin on gastric tissue exposed to low- and high-dose rate radiotherapy. Methods: Rats were randomly divided into control (n = 8), low-dose rate radiotherapy (LwDRR; n = 8; 8 Gy at 400 MU/min), high-dose rate radiotherapy (HgDRR; n = 8; 8 Gy at 1400 MU/min), and corresponding melatonin-treated groups (LwDRR + Mel; n = 8 and HgDRR + Mel; n = 8). Melatonin (50 mg/kg) was administered intraperitoneally 15 min before irradiation. Animals were sacrificed 48 h after treatment. Gastric tissues were evaluated histopathologically using H&E and PAS staining, oxidative DNA damage was assessed via 8-OHdG immunolocalization, and biochemical markers including TNF-α, IL-10, TAS, TOS, and OSI were analyzed. Results: Both radiotherapy protocols significantly induced gastric tissue injury, characterized by histopathological alterations, increased oxidative DNA damage, and elevated inflammatory and oxidative stress markers. 8-OHdG expression and TNF-α, TOS, and OSI levels were significantly increased in irradiated groups, whereas TAS levels were reduced, particularly under high-dose rate irradiation. Melatonin administration markedly attenuated these alterations by reducing histopathological damage, decreasing 8-OHdG expression and oxidative stress markers, and increasing anti-inflammatory IL-10 levels. No significant differences were observed between low- and high-dose rate radiotherapy in any measured parameter. Conclusion: Melatonin effectively mitigates radiation-induced gastric injury by modulating oxidative stress, inflammatory responses, and oxidative DNA damage. Collectively, these results suggest that melatonin may serve as a promising adjunctive radioprotective agent for preserving healthy gastrointestinal tissues during radiotherapy.