Zhou Xiaoliang, Li Deguan, Xu Wenqing, Zhang Heng, Wang Hao, Perdew Gary H
Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Department of Veterinary and Biomedical Sciences, The Center for Molecular Toxicology and Carcinogenesis, 309 LSB, The Pennsylvania State University, University Park, PA 16802, USA.
Antioxidants (Basel). 2020 Dec 12;9(12):1264. doi: 10.3390/antiox9121264.
Radiotherapy induced gastrointestinal syndrome results from the acute damage of intestinal stem cells, impaired crypts reconstruction, and subsequent breakdown of the mucosal barrier. The toxicity of ionizing radiation is associated with oxidative stress in the intestinal epithelial cells (IECs). Moreover, the rapid proliferation of IECs is a risk factor for radiation damage. β-naphthoflavone (BNF) is an agonist of the aryl hydrocarbon receptor (AhR) and possesses potential antioxidative activity. We investigated BNF radioprotection in IECs experiencing γ-ray exposure, contributed to mitigation of radiation enteritis. BNF significantly enhanced cell viability and suppressed cell apoptosis in an AhR activation-dependent manner. The mechanism of BNF reducing the IECs radiosensitivity was associated with cell cycle arrest and suppression of cell proliferation. In contrast, AhR antagonist CH-223191 significantly blocked BNF-induced cell cycle arrest. mRNA levels are induced after irradiation in a dose-dependent manner, and CYP1A1 protein expression increased in the irradiated intestinal tract as well. BNF also reduces DNA strand breaks induced by irradiation. These studies demonstrate that BNF pretreatment prolonged median survival time of mice upon exposure to a lethal dose of radiation and alleviated irradiation-induced toxicity within the bowel.
放射治疗引起的胃肠道综合征是由肠干细胞的急性损伤、隐窝重建受损以及随后的黏膜屏障破坏所致。电离辐射的毒性与肠上皮细胞（IECs）中的氧化应激有关。此外，IECs的快速增殖是辐射损伤的一个危险因素。β-萘黄酮（BNF）是芳烃受体（AhR）的激动剂，具有潜在的抗氧化活性。我们研究了BNF对受γ射线照射的IECs的辐射防护作用，有助于减轻放射性肠炎。BNF以AhR激活依赖的方式显著提高细胞活力并抑制细胞凋亡。BNF降低IECs放射敏感性的机制与细胞周期停滞和细胞增殖抑制有关。相反，AhR拮抗剂CH-223191显著阻断了BNF诱导的细胞周期停滞。照射后mRNA水平呈剂量依赖性诱导，照射肠道中的CYP1A1蛋白表达也增加。BNF还减少了辐射诱导的DNA链断裂。这些研究表明，BNF预处理可延长小鼠在接受致死剂量辐射后的中位生存时间，并减轻肠道内的辐射诱导毒性。
