Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Sci. 2022 Apr 22;23(9):4643. doi: 10.3390/ijms23094643.
The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated GI recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques were divided into two groups; eight received vehicle and eight GT3 24 h prior to 12 Gy TBI. Proximal jejunum was assessed for structural injuries and crypt survival on day 4 and 7. Apoptotic cell death and crypt cell proliferation were assessed with TUNEL and Ki-67 immunostaining. Irradiation induced significant shortening of the villi and reduced mucosal surface area. GT3 induced an increase in crypt depth at day 7, suggesting that more stem cells survived and proliferated after irradiation. GT3 did not influence crypt survival after irradiation. GT3 treatment caused a significant decline in TUNEL-positive cells at both day 4 (p < 0.03) and 7 (p < 0.0003). Importantly, GT3 induced a significant increase in Ki-67-positive cells at day 7 (p < 0.05). These data suggest that GT3 has radioprotective function in intestinal epithelial and crypt cells. GT3 should be further explored as a prophylactic medical countermeasure for radiation-induced GI injury.
胃肠道（GI）系统对辐射高度敏感。目前，尚无经食品和药物管理局（FDA）批准的用于治疗 GI 辐射损伤的医疗对策。维生素 E 类似物γ-生育三烯酚（GT3）是一种有前途的小鼠和非人灵长类动物（NHP）的辐射防护剂。我们评估了 GT3 对全身照射（TBI）NHP 的 GI 恢复的影响。将 16 只恒河猴分为两组；8 只在接受 12Gy TBI 前 24 小时接受载体，8 只接受 GT3。第 4 天和第 7 天评估近端空肠的结构损伤和隐窝存活。用 TUNEL 和 Ki-67 免疫染色评估凋亡细胞死亡和隐窝细胞增殖。照射导致绒毛明显缩短和粘膜表面积减少。GT3 在第 7 天诱导隐窝深度增加，表明照射后更多的干细胞存活并增殖。GT3 对照射后的隐窝存活没有影响。GT3 治疗在第 4 天（p<0.03）和第 7 天（p<0.0003）均导致 TUNEL 阳性细胞数量显著下降。重要的是，GT3 在第 7 天诱导 Ki-67 阳性细胞显著增加（p<0.05）。这些数据表明 GT3 对肠上皮和隐窝细胞具有放射防护作用。GT3 应作为预防辐射诱导的 GI 损伤的医疗对策进一步探索。
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