Protective role of alpha-phenyl-N-t-butylnitrone against ionizing radiation in U937 cells and mice.
Protective role of alpha-phenyl-N-t-butylnitrone against ionizing radiation in U937 cells and mice.
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发表时间：
2003-10
期刊：
影响因子：
11.2
通讯作者：
J. Lee;Jeen-Woo Park
中科院分区：
文献类型：
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作者：
J. Lee;Jeen-Woo Park
电离辐射（IR）会诱导活性氧（ROS）的产生，这在辐射损伤中起着重要的致病作用。 α-苯基-N-叔丁基硝酮 (PBN) 是最广泛使用的自旋捕获化合物之一，用于研究生物系统中自由基的存在。我们研究了 PBN 对 U937 细胞和小鼠 IR 的保护作用。暴露于红外线后，对照细胞和用 PBN 预处理的细胞在活力、细胞氧化还原状态和细胞氧化损伤方面存在明显差异。当细胞暴露于红外线时，用PBN处理的细胞中的脂质过氧化、氧化DNA损伤和蛋白质氧化显着降低。尽管PBN处理的细胞和对照细胞中抗氧化酶的活性相当，但与PBN处理的细胞相比，对照细胞的[GSSG]:[GSH + GSSG]比率和细胞内ROS的产生较高，而[NADPH]:[NADP(+) + NADPH]比率较低。与PBN处理的细胞相比，对照细胞中IR诱导的线粒体损伤（表现为线粒体通透性转变的改变、ROS积累的增加、ATP产生的减少以及形态变化）显着更高。 PBN 给药 14 天，每日剂量 30 mg/kg，为暴露于全身辐射的小鼠提供了显着的保护，防止死亡和氧化损伤。这些数据表明PBN作为一类新型体内不含硫辐射防护剂可能具有巨大的应用潜力。
Ionizing radiation (IR) induces the production of reactive oxygen species (ROS), which play an important causative role in radiation damage. alpha-Phenyl-N-t-butylnitrone (PBN) is one of the most widely used spin-trapping compounds for investigating the existence of free radicals in biological systems. We investigated the protective role of PBN against IR in U937 cells and mice. On exposure to IR, there was a distinct difference between the control cells and the cells pretreated with PBN in regard to viability, cellular redox status, and oxidative damage to cells. Lipid peroxidation, oxidative DNA damage, and protein oxidation were significantly lower in the cells treated with PBN when the cells were exposed to IR. Although the activities of antioxidant enzymes were comparable in PBN-treated and control cells, the [GSSG]:[GSH + GSSG] ratio and the generation of intracellular ROS were higher and the [NADPH]:[NADP(+) + NADPH] ratio was lower in control cells compared with PBN-treated cells. The IR-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of ROS, the reduction of ATP production, and the morphological change were significantly higher in control cells compared with PBN-treated cells. PBN administration for 14 days with a daily dosage of 30 mg/kg provided substantial protection against killing and oxidative damage to mice exposed to whole body irradiation. These data indicate that PBN may have great application potential as a new class of in vivo, nonsulfur-containing radiation protector.