Polypharmacy to Mitigate Acute and Delayed Radiation Syndromes.
Polypharmacy to Mitigate Acute and Delayed Radiation Syndromes.
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DOI：
10.3389/fphar.2021.634477
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发表时间：
2021
影响因子：
5.6
通讯作者：
Medhora M
中科院分区：
文献类型：
--
作者：
Gasperetti T;Miller T;Gao F;Narayanan J;Jacobs ER;Szabo A;Cox GN;Orschell CM;Fish BL;Medhora M
需要采取对策来减轻致命性急性辐射综合症(ARS)和急性辐射暴露的延迟效应(DEARE)。在WAG/RijCmcr大鼠中，ARS在全身照射(TBI)后30天发生，并分别在>；12.5和>；7小时后表现为潜在的致命性胃肠道(GI)和造血(H-ARS)毒性。DeARE包括潜在的致命性肺和肾损伤，在全身部分照射后观察到12.5Gy射线，一条后肢被屏蔽(无腿PBI)。这项研究的目的是通过多药联用提高ARS和DeARE的存活率，因为没有单一疗法显示出减轻这两组损伤的效果。为减轻7.5GyTBI后急性呼吸窘迫综合征(ARS)的发生，对三种造血生长因子(聚乙二醇人粒细胞集落刺激因子(HG-CSF)、聚乙二醇鼠粒细胞-巨噬细胞集落刺激因子(MGM-CSF)和聚乙二醇人白细胞介素11(hIL-11))在H-ARS小鼠模型中的联合应用进行了研究。这种三联疗法(TC)将30天的存活率从∼的25%提高到了60%。然后将TC与已证实的治疗GI-ARS和DEARE的药物相结合，即恩诺沙星、生理盐水和血管紧张素转换酶抑制剂赖诺普利。ARS和DeARE缓释剂的这种组合提高了7.5GyTBI或13GyPBI后GI-ARS、H-ARS和DeARE的存活率。TC+赖诺普利治疗后循环血细胞恢复及肺、肾功能也得到改善。综上所述，这些结果证明了一种有效的多药联用，以减轻辐射诱导的大鼠ARS和DeARE。
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.
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卡托普利的给药时间决定了全身辐射小鼠模型中的辐射防护或辐射敏化。
影响因子：
2.6
作者：
Davis, Thomas A.;Landauer, Michael R.;Mog, Steven R.;Barshishat-Kupper, Michal;Zins, Stephen R.;Amare, Mihret F.;Day, Regina M.
通讯作者：
Day, Regina M.
影响因子：
3.6
作者：
Bracci, Stefano;Valeriani, Maurizio;Osti, Mattia F.
通讯作者：
Osti, Mattia F.
影响因子：
3.4
作者：
Gao F;Fish BL;Moulder JE;Jacobs ER;Medhora M
通讯作者：
Medhora M
影响因子：
2.7
作者：
DiCarlo, Andrea L.;Maher, Carmen;Hick, John L.;Hanfling, Dan;Dainiak, Nicholas;Chao, Nelson;Bader, Judith L.;Coleman, C. Norman;Weinstock, David M.
通讯作者：
Weinstock, David M.
DOI：
10.1016/j.mrrev.2016.07.003
发表时间：
2016-10
期刊：
Mutation research. Reviews in mutation research
影响因子：
--
作者：
Boerma M;Sridharan V;Mao XW;Nelson GA;Cheema AK;Koturbash I;Singh SP;Tackett AJ;Hauer-Jensen M
通讯作者：
Hauer-Jensen M