Fairley Lauren H, Das Shatarupa, Dharwal Vivek, Amorim Nadia, Hegarty Karl J, Wadhwa Ridhima, Mounika Guntipally, Hansbro Philip M
Centre for Inflammation, School of Life Sciences, Faculty of Science, Centenary Institute and University of Technology Sydney, Sydney, NSW 2050, Australia.
Discipline of Pharmacy, Graduate School of Health, Faculty of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Antioxidants (Basel). 2023 Apr 21;12(4):973. doi: 10.3390/antiox12040973.
Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of oxidants in the form of reactive oxygen species (ROS). Mitochondria, the major producers of ROS, exhibit impaired structure and function in COPD, resulting in reduced oxidative capacity and excessive ROS production. Antioxidants have been shown to protect against ROS-induced oxidative damage in COPD, by reducing ROS levels, reducing inflammation, and protecting against the development of emphysema. However, currently available antioxidants are not routinely used in the management of COPD, suggesting the need for more effective antioxidant agents. In recent years, a number of mitochondria-targeted antioxidant (MTA) compounds have been developed that are capable of crossing the mitochondria lipid bilayer, offering a more targeted approach to reducing ROS at its source. In particular, MTAs have been shown to illicit greater protective effects compared to non-targeted, cellular antioxidants by further reducing apoptosis and offering greater protection against mtDNA damage, suggesting they are promising therapeutic agents for the treatment of COPD. Here, we review evidence for the therapeutic potential of MTAs as a treatment for chronic lung disease and discuss current challenges and future directions.
氧化应激是慢性阻塞性肺疾病（COPD）的一个主要特征，它会引发炎症信号传导、导致皮质类固醇抵抗、造成DNA损伤，并加速肺衰老和细胞衰老。有证据表明，氧化损伤不仅源于吸入刺激性物质的外源性暴露，还源于以活性氧（ROS）形式存在的内源性氧化剂。线粒体是ROS的主要产生部位，在COPD中其结构和功能受损，导致氧化能力降低和ROS产生过多。抗氧化剂已被证明可通过降低ROS水平、减轻炎症以及预防肺气肿的发展，来保护机体免受COPD中ROS诱导的氧化损伤。然而，目前可用的抗氧化剂并未常规用于COPD的治疗，这表明需要更有效的抗氧化剂。近年来，已开发出多种线粒体靶向抗氧化剂（MTA）化合物，它们能够穿过线粒体脂质双层，为从源头上减少ROS提供了一种更具针对性的方法。特别是，与非靶向的细胞抗氧化剂相比，MTA已被证明能通过进一步减少细胞凋亡和提供更强的针对线粒体DNA损伤的保护作用，从而发挥更大的保护作用，这表明它们是治疗COPD的有前景的治疗药物。在此，我们综述了MTA作为慢性肺部疾病治疗方法的治疗潜力的证据，并讨论了当前的挑战和未来的方向。
