A manganese porphyrin complex is a novel radiation protector
A manganese porphyrin complex is a novel radiation protector
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DOI：
10.1016/j.freeradbiomed.2004.04.029
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发表时间：
2004-07-15
影响因子：
7.4
通讯作者：
Park, JW
中科院分区：
文献类型：
--
作者：
Lee, JH;Park, JW
细胞暴露于电离辐射导致活性氧物质的形成，这与辐射诱导的细胞毒性有关。因此，抑制活性氧的化合物可赋予辐射防护作用。超氧化物歧化酶（SOD）模拟物已被证明是对由活性氧引起的细胞损伤的保护。本研究的目的是探讨锰（III）四（N-甲基-2-吡啶基）卟啉（MnTMPyP），一种细胞渗透性的SOD模拟物，辐射依赖性毒性的影响。我们研究了MnTMPyP在U937细胞和小鼠中对电离辐射的保护作用。暴露于电离辐射，有一个明显的差异，对照细胞和细胞预处理MnTMPyP的活力，细胞的氧化还原状态，和氧化损伤细胞。当细胞暴露于电离辐射时，用MnTMPyP处理的细胞中的脂质过氧化、氧化性DNA损伤和蛋白质氧化显著降低。与MnTMPyP处理的细胞相比，对照细胞的[GSSG]/[GSH + GSSG]比值和细胞内活性氧的产生较高，[NADPH]/[NADP+ + NADPH]比值较低。电离辐射引起的线粒体损伤，所反映的改变线粒体通透性转换，增加活性氧的积累，减少ATP的生产，和形态学的变化，是显着高于在MnTMPyP处理的细胞在对照细胞。以5 mg/kg的日剂量施用MnTMPyP 14天，在暴露于全身照射的小鼠中提供了针对杀伤和氧化损伤的实质性保护。这些数据表明，MnTMPyP作为一类新的在体内的，不含硫的辐射防护剂可能具有很大的应用潜力。(C)2004年爱思唯尔公司All rights reserved.
Exposure of cells to ionizing radiation leads to formation of reactive oxygen species, which are associated with radiation-induced cytotoxicity. Therefore, compounds that scavenge reactive oxygen species may confer radioprotective effects. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. The objective of this study was to investigate the effects of manganese(III) tetrakis(N-methyl-2pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on radiation-dependent toxicity. We investigated the protective role of MnTMPyP against ionizing radiation in U937 cells and mice. On exposure to ionizing radiation, there was a distinct difference between control cells and cells pretreated with MnTMPyP with respect 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 MnTMPyP when the cells were exposed to ionizing radiation. The [GSSG]/[GSH + GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP+ + NADPH] ratio was lower in control cells compared with MnTMPyP-treated cells. Ionizing radiation-induced mitochondrial damage, as reflected by the altered mitochondrial permeability transition, increase in accumulation of reactive oxygen species, reduction of ATP production, and morphological change, was significantly higher in control cells than in MnTMPyP-treated cells. MnTMPyP administration for 14 days at a daily dosage of 5 mg/kg provided substantial protection against killing and oxidative damage in mice exposed to whole-body irradiation. These data indicate that MnTMPyP may have great application potential as a new class of in vivo, non-sulfur-containing radiation protectors. (C) 2004 Elsevier Inc. All rights reserved.