Exposure to high doses of radiation, accidental or therapeutic, often results in gastrointestinal (GI) injury. To date, there are no therapies available to mitigate GI injury after radiation exposure. Gamma-tocotrienol (GT3) is a promising radioprotector under investigation in nonhuman primates (NHP). We have shown that GT3 has radioprotective function in intestinal epithelial and crypt cells in NHPs exposed to 12 Gy total-body irradiation (TBI). Here, we determined GT3 potential in accelerating the GI recovery in partial-body irradiated (PBI) NHPs using X-rays, sparing 5% bone marrow. Sixteen rhesus macaques were treated with either vehicle or GT3 24 h prior to 12 Gy PBI. Structural injuries and crypt survival were examined in proximal jejunum on days 4 and 7. Plasma citrulline was assessed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Crypt cell proliferation and apoptotic cell death were evaluated using Ki-67 and TUNEL staining. PBI significantly decreased mucosal surface area and reduced villous height. Interestingly, GT3 increased crypt survival and enhanced stem cell proliferation at day 4; however, the effects seemed to be minimized by day 7. GT3 did not ameliorate a radiation-induced decrease in citrulline levels. These data suggest that X-rays induce severe intestinal injury post-PBI and that GT3 has minimal radioprotective effect in this novel model.

中文翻译：

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γ-生育三烯酚对非人灵长类动物模型中局部辐射引起的肠损伤的影响


意外或治疗性暴露于高剂量辐射通常会导致胃肠道 (GI) 损伤。迄今为止，还没有任何疗法可以减轻辐射暴露后的胃肠道损伤。 γ-生育三烯酚 (GT3) 是一种有前途的辐射防护剂，正在非人灵长类动物 (NHP) 中进行研究。我们已经证明 GT3 对暴露于 12 Gy 全身照射 (TBI) 的 NHP 的肠上皮和隐窝细胞具有辐射防护功能。在这里，我们使用 X 射线确定了 GT3 在加速部分身体照射 (PBI) NHP 胃肠道恢复方面的潜力，并保留了 5% 的骨髓。在 12 Gy PBI 前 24 小时，用媒介物或 GT3 治疗 16 只恒河猴。第 4 天和第 7 天检查近端空肠的结构损伤和隐窝存活率。使用液相色谱-串联质谱 (LC-MS/MS) 评估血浆瓜氨酸。使用 Ki-67 和 TUNEL 染色评估隐窝细胞增殖和凋亡细胞死亡。 PBI显着减少了粘膜表面积并降低了绒毛高度。有趣的是，GT3 在第 4 天增加了隐窝存活并增强了干细胞增殖；然而，到第 7 天，这种影响似乎已降至最低。GT3 并没有改善辐射引起的瓜氨酸水平下降。这些数据表明，X 射线在 PBI 后会引起严重的肠道损伤，而 GT3 在这种新模型中的辐射防护作用微乎其微。