Garg Sarita, Garg Tarun K, Miousse Isabelle R, Wise Stephen Y, Fatanmi Oluseyi O, Savenka Alena V, Basnakian Alexei G, Singh Vijay K, Hauer-Jensen Martin
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.
Antioxidants (Basel). 2022 Sep 25;11(10):1895. doi: 10.3390/antiox11101895.
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.
意外或治疗性地暴露于高剂量辐射通常会导致胃肠道（GI）损伤。迄今为止，尚无可用疗法来减轻辐射暴露后的胃肠道损伤。γ-生育三烯酚（GT3）是一种有前景的辐射防护剂，正在非人灵长类动物（NHP）中进行研究。我们已经表明，GT3在接受12 Gy全身照射（TBI）的NHP的肠上皮细胞和隐窝细胞中具有辐射防护功能。在此，我们使用X射线确定了GT3在加速部分身体照射（PBI）的NHP的胃肠道恢复方面的潜力，保留5%的骨髓。16只恒河猴在接受12 Gy PBI前24小时用赋形剂或GT3进行治疗。在第4天和第7天检查近端空肠的结构损伤和隐窝存活情况。使用液相色谱-串联质谱法（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显著降低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天这些作用似乎最小化。GT3并未改善辐射诱导的瓜氨酸水平下降。这些数据表明，X射线在PBI后会导致严重的肠道损伤，并且在这个新模型中GT3具有最小的辐射防护作用。
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