A novel radioprotective mechanism of sodium orthovanadate and its application to radiotherapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07644
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: The University of Tokushima
• Principal Investigator: NISHIYAMA Yuichi 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (80730598)
• Co-Investigator(Kenkyū-buntansha): 森田 明典 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (90334234) ; 金井 昭教 東京大学, 大学院新領域創成科学研究科, 特任准教授 (60549567)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: バナデート / p53 / 血管内皮 / 遅発性腸管障害 / 炎症

Outline of Final Research Achievements

To investigate the mechanism of the p53-independent protective effect of vanadate against radiation-induced bone marrow injury, we performed a comprehensive analysis of gene expression in the bone marrow and kidney of Trp53 knockout mice after total-body irradiation. Vanadate tended to suppress the upregulation of inflammation-related gene expression, which may be associated with the p53-independent protective effect of vanadate against the bone marrow injury. Moreover, vanadate effectively suppressed delayed intestinal death in mice after fractionated caudal half-body irradiation, which is thought to be caused by vascular endothelial damage, suggesting that vanadate has a protective effect against vascular endothelial damage.

Free Research Field

放射線生物学

Academic Significance and Societal Importance of the Research Achievements

放射線骨髄障害に対するバナデートのp53非依存的な新規放射線防護効果として、炎症反応の制御が関与しているものと考えられた。これは、新たな放射線感受性修飾因子の発見につながるとともに、新規放射線防護剤の開発にも寄与するものと考える。
他方、バナデートは分割照射後の遅発性腸死を効果的に防ぐことが明らかとなり、骨盤部放射線治療で生じる直腸炎などの晩期障害を防ぐ有望な防護剤としての可能性が示された。