Mg ATP and antioxidants augment the radioprotective effect of surfactant copolymers.
Mg ATP and antioxidants augment the radioprotective effect of surfactant copolymers.
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DOI：
10.1097/hp.0b013e3182166759
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发表时间：
2011-12
期刊：
影响因子：
2.2
通讯作者：
Lee RC
中科院分区：
文献类型：
--
作者：
Soneru AP;Beckett MA;Weichselbaum RR;Lee RC
高强度电离辐射对组织的损伤效应在活性氧的介导下，具有剂量、频率、氧浓度和组织性质的依赖性。高强度电离辐射可通过膜脂过氧化导致膜破裂，导致细胞迅速坏死。这导致跨膜离子梯度的丧失和随后细胞内ATP存储的耗尽，随后细胞内产生了活性氧物种。当细胞膜广泛破裂时，急性细胞坏死随之而来。三嵌段共聚物表面活性剂，如泊洛沙姆188(P188)，能够封闭受损的横纹肌细胞膜，提高辐射后的生存能力。分离的大鼠横纹肌肉细胞接受40Gy1.5Gymin−1的照射，20min后用p188、N-乙酰半胱氨酸和镁-三磷酸腺苷的组合排列处理。用钙黄素-AM和乙锭-Homodimer-1染色检测细胞在18和48h的存活率。在照射后18小时，联合应用p188、ATP和NAC使细胞存活率恢复到接近60%的假暴露水平。在照射后48小时，细胞存活率大幅下降到7%-20%的范围，无论尝试干预。然而，在48小时的时间点上，p188、ATP和NAC的组合使细胞活力增加了一倍以上。8 kDa聚乙二醇组和10 kDa中性葡聚糖组均不能有效提高细胞存活率。这些结果表明，抗氧化剂和细胞能量底物提高了膜密封共聚表面活性剂在延长大规模辐射后细胞存活率方面的有效性。
Mediated by reactive oxygen species, the damaging effects of high-intensity ionizing irradiation on tissues are dose, frequency, oxygen concentration and tissue property dependent. Intense ionizing irradiation exposure may cause rapid cellular necrosis by peroxidation of membrane lipids leading to membrane disruption. This leads to a loss of the transmembrane ionic gradients and a subsequent depletion of the cellular ATP store, followed by cellular generation of reactive oxygen species. When membrane disruption is extensive, acute cellular necrosis follows. Triblock copolymer surfactants, such as Poloxamer 188 (P188), are able to seal damaged rhabdomyocyte membranes, increasing post-irradiation viability. Separated rat rhabdomyocytes were exposed to 40 Gy (60Co 1.5 Gy min−1) irradiation and treated at 20 minutes with combination permutations of P188, N-acetylcysteine (NAC) and Mg-ATP. Cell viability at 18 and 48 hours was determined using Calcein-AM and Ethidium Homodimer-1 staining. At 18 hours after irradiation, the combined administration of P188, ATP, and NAC restored cell viability rates to near sham-exposed levels of 60%. At 48 hours post-irradiation, cell viability dropped substantially to the 7%–20% range, regardless of attempted intervention. Nevertheless, the combination of P188, ATP and NAC more than doubled cell viability at the 48-hour time point. Neither 8 kDa polyethylene glycol nor 10 kDa neutral dextran were as effective in enhancing cell viability. These results indicate that antioxidants and cellular energy substrates improve the efficacy of membrane-sealing copolymer surfactants in prolonging cellular viability following massive radiation exposure.