期刊论文详细信息
Frontiers in Pharmacology
Polypharmacy to Mitigate Acute and Delayed Radiation Syndromes
George N. Cox1  Christie M. Orschell3  Tessa Miller6  Brian L. Fish6  Jayashree Narayanan6  Feng Gao6  Tracy Gasperetti6  Meetha Medhora7  Elizabeth R. Jacobs7  Aniko Szabo8 
[1] Bolder BioTechnology Inc., Boulder, CO, United States;Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States;Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States;Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States;Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States;Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States;Department of Veterans Affairs, Research Service, Zablocki VAMC, Milwaukee, WI, United States;Institute for Health and Equity, Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, United States;
关键词: polypharmacy;    acute radiation syndrome;    delayed effects of acute radiation exposure;    mitigation;    hematopoietic growth factor;    lisinopril;   
DOI  :  10.3389/fphar.2021.634477
来源: DOAJ
【 摘 要 】

There is a need for countermeasures to mitigate lethal acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE). In WAG/RijCmcr rats, ARS occurs by 30-days following total body irradiation (TBI), and manifests as potentially lethal gastrointestinal (GI) and hematopoietic (H-ARS) toxicities after >12.5 and >7 Gy, respectively. DEARE, which includes potentially lethal lung and kidney injuries, is observed after partial body irradiation >12.5 Gy, with one hind limb shielded (leg-out PBI). The goal of this study is to enhance survival from ARS and DEARE by polypharmacy, since no monotherapy has demonstrated efficacy to mitigate both sets of injuries. For mitigation of ARS following 7.5 Gy TBI, a combination of three hematopoietic growth factors (polyethylene glycol (PEG) human granulocyte colony-stimulating factor (hG-CSF), PEG murine granulocyte-macrophage-CSF (mGM-CSF), and PEG human Interleukin (hIL)-11), which have shown survival efficacy in murine models of H-ARS were tested. This triple combination (TC) enhanced survival by 30-days from ∼25% to >60%. The TC was then combined with proven medical countermeasures for GI-ARS and DEARE, namely enrofloxacin, saline and the angiotensin converting enzyme inhibitor, lisinopril. This combination of ARS and DEARE mitigators improved survival from GI-ARS, H-ARS, and DEARE after 7.5 Gy TBI or 13 Gy PBI. Circulating blood cell recovery as well as lung and kidney function were also improved by TC + lisinopril. Taken together these results demonstrate an efficacious polypharmacy to mitigate radiation-induced ARS and DEARE in rats.

【 授权许可】

Unknown   

  文献评价指标  
  下载次数:0次 浏览次数:0次