Stomatology Department, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, China; Stomatology Department, Chengdu Shuangliu Hospital of Traditional Chinese Medicine, Chengdu, 610212, China.
Stomatology Department, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, China.
Free Radic Biol Med. 2023 Aug 1;204:84-94. doi: 10.1016/j.freeradbiomed.2023.04.020. Epub 2023 Apr 28.
Radiation-induced oral mucositis (RIOM) is considered to be the most common acute side effect of radiation therapy and occurs during intentional or accidental radiation exposure. Antioxidant synthesis agents have been reported to protect against or alleviate the development of mucositis, but the resulting side effects of chemical synthesis agents limit their use in clinical practice. Lycium barbarum polysaccharide-glycoprotein (LBP), a polysaccharide extract of the Lycium barbarum fruit, has superior antioxidant capacity and biosafety and is a potential option for radiation prevention and treatment. Here, we aimed to investigate whether LBP conferred radioprotection against ionizing radiation-induced oral mucosal damage. We found that LBP exerted radioprotective effects in irradiated HaCaT cells, improving cell viability, stabilizing mitochondrial membrane potential, and decreasing cell death. LBP pretreatment reduced oxidative stress and ferroptosis in radioactivity-damaged cells by activating the transcription factor Nrf2 and promoting its downstream targets, such as HO-1, NQO1, SLC7A11, and FTH1. Knockdown of Nrf2 eliminated the protective effects of LBP, implying the essential role of Nrf2 in LBP activity. Additionally, the topical application of LBP thermosensitive hydrogel on rat mucosa resulted in a significant decrease in ulcer size in the irradiated group, suggesting that LBP oral mucoadhesive gel may be a potential tool for the treatment of irradiation. In conclusion, we demonstrated that LBP attenuates ionizing radiation-induced oral mucosa injury by reducing oxidative stress and inhibiting ferroptosis via the Nrf2 signaling pathway. LBP may be a promising medical countermeasure against RIOM.
辐射诱导的口腔粘膜炎（RIOM）被认为是放射治疗最常见的急性副作用，发生在故意或意外辐射暴露期间。抗氧化合成剂已被报道可预防或减轻粘膜炎的发展，但化学合成剂的副作用限制了它们在临床实践中的应用。枸杞多糖糖蛋白（LBP）是枸杞果实的多糖提取物，具有卓越的抗氧化能力和生物安全性，是辐射预防和治疗的潜在选择。在这里，我们旨在研究 LBP 是否对电离辐射诱导的口腔粘膜损伤具有放射防护作用。我们发现 LBP 对放射性损伤的 HaCaT 细胞发挥了放射防护作用，提高了细胞活力，稳定了线粒体膜电位，减少了细胞死亡。LBP 预处理通过激活转录因子 Nrf2 并促进其下游靶标，如 HO-1、NQO1、SLC7A11 和 FTH1，减少了放射性损伤细胞中的氧化应激和铁死亡。Nrf2 的敲低消除了 LBP 的保护作用，这表明 Nrf2 在 LBP 活性中起着重要作用。此外，LBP 热敏水凝胶在大鼠粘膜上的局部应用导致照射组溃疡面积显著减小，这表明 LBP 口腔粘膜黏附凝胶可能是治疗照射的一种有潜力的工具。总之，我们证明 LBP 通过减少氧化应激和抑制铁死亡来减轻电离辐射引起的口腔粘膜损伤，通过 Nrf2 信号通路。LBP 可能是 RIOM 的一种有前途的医疗对策。
