Reactive oxygen species damage drives cardiac and mitochondrial dysfunction following acute nano-titanium dioxide inhalation exposure.
Reactive oxygen species damage drives cardiac and mitochondrial dysfunction following acute nano-titanium dioxide inhalation exposure.
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急性纳米二乙二醇吸入暴露后，活性氧损伤驱动心脏和线粒体功能障碍。
DOI：
10.1080/17435390.2017.1416202
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发表时间：
2018-03
期刊：
影响因子：
5
通讯作者：
Hollander JM
中科院分区：
文献类型：
--
作者：
Nichols CE;Shepherd DL;Hathaway QA;Durr AJ;Thapa D;Abukabda A;Yi J;Nurkiewicz TR;Hollander JM
纳米技术为从化妆品到药物输送的产品提供了创新，从而增加了工程纳米材料（ENM）的暴露。不幸的是，环境营养学对健康的影响没有得到充分认识。二氧化钛（TiO 2）是最广泛生产的ENM之一，因为它在许多应用中使用。肺暴露后的肺外效应已经确定，可能涉及活性氧（ROS）。本研究的目的是确定ROS对心脏功能的影响程度以及纳米TiO 2暴露后ROS的影响程度。为了解决这个问题，我们利用了一个转基因小鼠模型与过表达的一种新的神经靶向的抗氧化酶（磷脂氢谷胱甘肽过氧化物酶; mPHGPx），它提供了对脂质膜的氧化应激保护。将MPHGPx小鼠和同窝对照暴露于纳米TiO 2气溶胶（Evonik，P25），以提供11μg/小鼠的计算肺沉积。暴露后24小时，我们观察到舒张功能障碍，如E/A比值大于2所证明的，并且野生型小鼠在舒张期间径向应变增加（两者均P<0.05），指示限制性充盈。mPHGPx的过表达减轻了nano-TiO 2暴露引起的收缩缺陷。为了研究与所观察到的心功能不全相关的细胞机制，我们将注意力集中在心肌细胞上。我们观察到纳米TiO 2暴露后mPHGPx转基因小鼠的ROS产生显著增加（P <0.05），线粒体呼吸功能降低（P<0.05）。总之，纳米TiO 2吸入暴露与心脏舒张功能障碍和线粒体功能改变相关，这可以通过mPHGPx的过表达来减轻，表明ROS在收缩和生物能量学功能障碍的发展中起作用。
Nanotechnology offers innovation in products from cosmetics to drug delivery, leading to increased engineered nanomaterial (ENM) exposure. Unfortunately, health impacts of ENM are not fully realized. Titanium Dioxide (TiO2) is among the most widely produced ENM due to its use in numerous applications. Extrapulmonary effects following pulmonary exposure have been identified and may involve reactive oxygen species (ROS). The goal of this study was to determine the extent of ROS involvement on cardiac function and the mitochondrion following nano-TiO2 exposure. To address this question, we utilized a transgenic mouse model with overexpression of a novel mitochondrially-targeted antioxidant enzyme (phospholipid hydroperoxide glutathione peroxidase; mPHGPx) which provides protection against oxidative stress to lipid membranes. MPHGPx mice and littermate controls were exposed to nano-TiO2 aerosols (Evonik, P25) to provide a calculated pulmonary deposition of 11μg/mouse. Twenty-four hours following exposure, we observed diastolic dysfunction as evidenced by E/A ratios greater than 2 and increased radial strain during diastole in wild-type mice (P<0.05 for both), indicative of restrictive filling. Overexpression of mPHGPx mitigated the contractile deficits resulting from nano-TiO2 exposure. To investigate the cellular mechanisms associated with the observed cardiac dysfunction, we focused our attention on the mitochondrion. We observed a significant increase in ROS production (P<0.05) and decreased mitochondrial respiratory function (P<0.05) following nano-TiO2 exposure which were attenuated in mPHGPx transgenic mice. In summary, nano-TiO2 inhalation exposure is associated with cardiac diastolic dysfunction and mitochondrial functional alterations, which can be mitigated by the overexpression of mPHGPx, suggesting ROS contribution in the development of contractile and bioenergetics dysfunction.
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