Scholarlink

<p>Acute gastrointestinal radiation syndrome (GI-ARS) is a significant health threat following high-dose ionizing radiation (IR) exposure, leading to severe morbidity and mortality. The syndrome is characterized by gastrointestinal tissue damage caused by angiotensin II (Ang II) and reactive oxygen species (ROS), resulting in impaired GI function, systemic bacteremia, multi-organ failure, and eventual death. Dysregulation of the renin-angiotensin system (RAS) via Ang II exacerbates ROS production through activation of the Angiotensin II type 1 receptor (AT1R). This underscores the need for agents capable of both scavenging ROS and inhibiting AT1R activity. To address this, we developed YK-4–250, a Tempol-conjugated angiotensin receptor blocker (TCARB). YK-4–250 selectively inhibits the AT1R and exhibits antioxidant properties like Tempol and has a no observed adverse effect level (NOAEL) greater than 100&#xa0;mg/kg. A single daily oral dose of 20&#xa0;mg/kg of YK-4–250, administered either prior to or after 50% lethal dose (LD<sub>50</sub>) of partial body irradiation (PBI), improved overall survival significantly (by 25–30% above vehicle group) and enhanced GI function by day 7. Additionally, YK-4–250’s paramagnetic properties enable MRI monitoring, allowing visualization of drug delivery to target tissues. These findings suggest that YK-4–250 is a promising candidate for protecting and mitigating radiation-induced injury resulting in improved outcomes in GI-ARS.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

YK-4–250 mitigates gastrointestinal radiation syndrome and promotes overall survival following partial body radiation injury

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月26日

查看全文
  • Vidya P. Kumar,
  • Yali Kong,
  • Kan Wang,
  • Asa R. Britton-Jenkins,
  • Stanton Dulan,
  • Landon L. Moore,
  • Debra Saunders,
  • Randal May,
  • Rheal Towner,
  • Sanchita P. Ghosh,
  • Courtney W. Houchen,
  • Milton L. Brown

摘要

Acute gastrointestinal radiation syndrome (GI-ARS) is a significant health threat following high-dose ionizing radiation (IR) exposure, leading to severe morbidity and mortality. The syndrome is characterized by gastrointestinal tissue damage caused by angiotensin II (Ang II) and reactive oxygen species (ROS), resulting in impaired GI function, systemic bacteremia, multi-organ failure, and eventual death. Dysregulation of the renin-angiotensin system (RAS) via Ang II exacerbates ROS production through activation of the Angiotensin II type 1 receptor (AT1R). This underscores the need for agents capable of both scavenging ROS and inhibiting AT1R activity. To address this, we developed YK-4–250, a Tempol-conjugated angiotensin receptor blocker (TCARB). YK-4–250 selectively inhibits the AT1R and exhibits antioxidant properties like Tempol and has a no observed adverse effect level (NOAEL) greater than 100 mg/kg. A single daily oral dose of 20 mg/kg of YK-4–250, administered either prior to or after 50% lethal dose (LD50) of partial body irradiation (PBI), improved overall survival significantly (by 25–30% above vehicle group) and enhanced GI function by day 7. Additionally, YK-4–250’s paramagnetic properties enable MRI monitoring, allowing visualization of drug delivery to target tissues. These findings suggest that YK-4–250 is a promising candidate for protecting and mitigating radiation-induced injury resulting in improved outcomes in GI-ARS.