Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
Homi Bhabha National Institute, Mumbai, 400094, India.
Biol Trace Elem Res. 2017 Sep;179(1):130-139. doi: 10.1007/s12011-017-0955-9. Epub 2017 Feb 11.
The aim of the present study is to evaluate the radioprotective effect of low-dose selenium supplementation (multiple administrations) on radiation toxicities and mortality induced by lethal dose of whole-body irradiation (WBI). For this, BALB/c mice received sodium selenite (4 μg/kg body wt) intraperitoneally for five consecutive days and subjected to WBI at an absorbed dose of 8 Gy (Co, 1 Gy/min). Administration of sodium selenite was continued even during the post irradiation days three times a week till the end of the experiment. The radioprotective effect was evaluated in terms of the improvement in 30 days post irradiation survival, protection from DNA damage, and biochemical and histological changes in radiosensitive organs. The results indicated that low-dose sodium selenite administration did not protect the mice from radiation-induced hematopoietic and gastrointestinal injuries and subsequent mortality. However, it significantly prevented the radiation-induced genotoxicity or DNA damage in peripheral leukocytes. Further sodium selenite administration modulated the messenger RNA (mRNA) expression of GPx1, GPx2, and GPx4 in the spleen and intestine differentially and led to a significant increase in GPx activity (∼1.5 to 2-folds) in these organs. In line with this observation, sodium selenite administration reduced the level of lipid peroxidation in the intestine. In conclusion, our study shows that low-dose sodium selenite supplementation can be an effective strategy to prevent WBI-induced genotoxicity but may not have an advantage against mortality sustained during nuclear emergencies.
本研究旨在评估低剂量硒补充（多次给药）对致死剂量全身照射（WBI）诱导的辐射毒性和死亡率的放射防护作用。为此，BALB/c 小鼠连续 5 天腹腔内给予亚硒酸钠（4μg/kg 体重），并以 8Gy（Co，1Gy/min）的吸收剂量接受 WBI。即使在照射后 3 天，每周 3 次继续给予亚硒酸钠给药，直到实验结束。通过改善照射后 30 天的存活率、防止 DNA 损伤以及辐射敏感器官的生化和组织学变化来评估放射防护作用。结果表明，低剂量亚硒酸钠给药不能保护小鼠免受辐射引起的造血和胃肠道损伤以及随后的死亡。然而，它显著防止了外周血白细胞的辐射诱导的遗传毒性或 DNA 损伤。进一步的亚硒酸钠给药以不同的方式调节脾和肠中 GPx1、GPx2 和 GPx4 的信使 RNA（mRNA）表达，并导致这些器官中 GPx 活性（约 1.5 至 2 倍）显著增加。与此观察结果一致，亚硒酸钠给药降低了肠中脂质过氧化水平。总之，我们的研究表明，低剂量亚硒酸钠补充可能是预防 WBI 诱导的遗传毒性的有效策略，但在核紧急情况下维持死亡率方面可能没有优势。
