Overexpression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic lung injury
Overexpression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic lung injury
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DOI：
10.1016/j.rmed.2006.07.017
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发表时间：
2007-04-01
影响因子：
4.3
通讯作者：
Marunaka, Yoshinori
中科院分区：
文献类型：
--
作者：
Nagata, Kazuhiro;Iwasaki, Yoshinobu;Marunaka, Yoshinori
背景资料：动物暴露于高氧导致肺损伤，其特征在于弥漫性肺泡损伤和血浆渗出到肺泡腔中。活性氧在高氧肺损伤的发生发展中起重要作用。线粒体氧化磷酸化是ROS的主要来源之一。N-乙酰半胱氨酸（NAC）是谷胱甘肽（GSH）的前体，其通过将过氧化氢还原为水和醇而起抗氧化剂的作用。目的：探讨NAC对高氧肺损伤的保护作用及其机制。结果：吸入NAC后，小鼠肺组织匀浆中GSH含量明显升高，肺组织匀浆中GSH含量明显降低，肺组织匀浆中GSH含量明显升高。NAC还减弱了支气管肺泡灌洗液（BALF）和肺组织中的细胞浸润。吸入NAC可降低支气管肺泡灌洗液中的总蛋白水平和肺组织匀浆中脂质过氧化反应标志物8-异前列腺素的水平。吸入NAC可诱导MnSOD mRNA和蛋白的过度表达，但对CuZnSOD、细胞外SOD和谷胱甘肽过氧化物酶1等抗氧化酶的表达无明显影响。这些发现表明，NAC在高氧肺损伤中的抗氧化特性涉及与MnSOD诱导相关的线粒体ROS减少，除了它作为GSH前体作用外。(c)2006爱思唯尔有限公司保留所有权利。
Background: Exposure of animals to hyperoxia causes lung injury, characterized by diffuse alveolar damage and exudation of plasma into the alveolar space. Reactive oxygen species (ROS) play an important role in the development of hyperoxic lung injury. Mitochondrial oxidative phosphorylation is one of the major sources of ROS. N-acetylcysteine (NAC) is a precursor of glutathione (GSH), which functions as an antioxidant by reducing hydrogen peroxide to water and alcohols. NAC has been shown to diminish lung injury in a large variety of animal models.Aim: We elucidated the mechanism underlying the protective effects of NAC in hyperoxia-induced lung injury.Methods: Mate BALB/c mice were exposed to 98% oxygen for 72 h. The mice inhaled NAC or saline twice a day from 72 h before oxygen exposure to the end of experiment.Results: Inhaled NAC increased the GSH level in lung homogenate. NAC also attenuated cellular infiltrations in both bronchoatveotar lavage fluid (BALF) and lung tissue. The total protein level in BALF and the level of 8-isoprostane, a marker of lipid peroxidation, in lung homogenate were decreased by inhalation of NAC. Inhaled NAC induced the overexpression of Mn superoxide dismutase (MnSOD) mRNA and protein, but did not alter the expressions of other antioxidant enzymes, including CuZnSOD, extracellular SOD, and glutathione peroxydase 1.Conclusion: These findings suggest that the antioxidant properties of NAC in hyperoxic lung injury involve a decrease in mitochondrial ROS in association with the induction of MnSOD, in addition to its rote as a precursor of GSH. (c) 2006 Elsevier Ltd. All rights reserved.