Establishment of Xanthine Oxidase Inhibitor Therapy for Hemorrhagic Shock under a Novel Indication

2024 Fiscal Year Final Research Report

• Project/Area Number: 20K17877
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Nippon Medical School
• Principal Investigator: Takiguchi Toru 日本医科大学, 医学部, 講師 (20787593)
• Project Period (FY): 2020-04-01 – 2025-03-31
• Keywords: 出血性ショック / 活性酸素 / 酸化ストレス / キサンチンオキシダーゼ阻害薬 / 抗酸化作用 / 抗炎症作用

Outline of Final Research Achievements

Acute lung injury following hemorrhagic shock is a major cause of organ failure in patients with severe trauma. The antioxidant effect of xanthine oxidase (XO) inhibitors may have a therapeutic role in mitigating this condition. In this study, we evaluated the effects of two XO inhibitors with different mechanisms of action (allopurinol and febuxostat) in a rat model of hemorrhagic shock. Compared to the control group, the XO inhibitor-treated groups showed significantly lower levels of uric acid, oxidative stress marker (MDA), and inflammatory cytokine (IL-6). Histopathological examination also revealed attenuated lung injury in the XO inhibitor-treated groups. These findings suggest that XO inhibitors exert antioxidant and anti-inflammatory effects in acute lung injury associated with hemorrhagic shock.

Free Research Field

救急医学

Academic Significance and Societal Importance of the Research Achievements

大量の出血で血圧が低下する「出血性ショック」の後に生じる肺障害は、重症外傷患者の命に関わる深刻な問題です。本研究では、体内の酸化ストレスを抑える薬（キサンチンオキシダーゼ阻害薬）が、この肺障害を改善できるかを動物実験で検討しました。その結果、炎症や細胞の傷害が軽減され、肺の状態が改善することが確認されました。本成果は、将来の新たな治療法につながる可能性があります。