Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice
Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice
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DOI：
10.1080/09553002.2021.1941377
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发表时间：
2021-06-28
影响因子：
2.6
通讯作者：
Aoki, Shin
中科院分区：
文献类型：
--
作者：
Nishiyama, Yuichi;Morita, Akinori;Aoki, Shin
目的本实验室前期研究表明，p53强抑制剂原钒酸钠（sodium orthovanadate，vanadate）能有效抑制12戈伊全身照射（total-body radiation，TBI）后小鼠造血系统（hematopoietic，HP）和胃肠道（gastrointestinal，GI）综合征的致死率。然而，这一结论与p53在肠上皮中起辐射防护作用的事实不一致。大约12戈伊的TBI后的死亡归因于HP和GI综合征的联合作用。为了验证预防性给予p53抑制剂对HP和GI综合征的保护作用，在本研究中，在TBI和下半身照射（部分体照射：PBI）小鼠模型中研究了钒酸盐的辐射保护作用。方法雌性ICR小鼠经尾静脉注射钒酸盐或溶媒，然后给予致死剂量的TBI或PBI。通过分析存活率、体重、造血参数以及骨髓和肠上皮的组织学变化来评价钒酸盐对辐射的防护作用。结果钒酸盐治疗能有效抑制TBI诱导的HP综合征。TBI后，钒酸盐处理的小鼠保留了更好的骨髓细胞结构，并显示出显着更高的生存率相比，溶剂处理的动物。相比之下，钒酸盐不能减轻肠隐窝的损失，也不能挽救PBI后胃肠道死亡的小鼠。结论钒酸盐是一种p53抑制剂，对HP有一定的放射防护作用，但对急性胃肠道放射损伤无明显防护作用。
Purpose Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models. Methods Female ICR mice were given a single injection of vanadate or vehicle, followed by a lethal dose of TBI or PBI. Radioprotective effects of vanadate against the irradiations were evaluated by analyzing survival rate, body weight, hematopoietic parameters, and histological changes in the bone marrow and intestinal epithelium. Results TBI-induced HP syndrome was effectively suppressed by vanadate treatment. After TBI, the vanadate-treated mice retained better bone marrow cellularity and showed markedly higher survival rate compared to the vehicle-treated animals. In contrast, vanadate did not relieve loss of intestinal crypts and failed to rescue mice from GI death after PBI. Conclusion Vanadate is a p53 inhibitor that has been shown to be beneficial as a radiation protective agent against HP but was not effective in protecting against acute GI radiation injury.