Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is the most abundant proinflammatory agent. Considerable evidence indicates that LPS challenge inescapably causes oxidative stress and mitochondrial dysfunction, leading to cell and tissue damage. Increased mitochondrial reactive oxygen species (mtROS) generation triggered by LPS is known to play a key role in the progression of the inflammatory response. mtROS at excessive levels impair electron transport chain functioning, reduce the mitochondrial membrane potential, and initiate lipid peroxidation and oxidative damage of mitochondrial proteins and mtDNA. Over the past 20 years, a large number of mitochondria-targeted antioxidants (mito-AOX) of different structures that can accumulate inside mitochondria and scavenge free radicals have been synthesized. Their protective role based on the prevention of oxidative stress and the restoration of mitochondrial function has been demonstrated in a variety of common diseases and pathological states. This paper reviews the current data on the beneficial application of different mito-AOX in animal endotoxemia models, in either in vivo or in vitro experiments. The results presented in our review demonstrate the promising potential of approaches based on mito-AOX in the development of new treatment strategies against Gram-negative infections and LPS per se.

中文翻译：

---

线粒体靶向抗氧化剂对脂多糖挑战的炎症反应的保护作用：审查。

脂多糖（LPS）是革兰氏阴性细菌外膜的主要成分，是最丰富的促炎剂。大量证据表明，LPS攻击不可避免地会引起氧化应激和线粒体功能障碍，从而导致细胞和组织损伤。已知由LPS触发的线粒体活性氧（mtROS）生成增加在炎症反应的进程中起关键作用。过量的mtROS会损害电子传输链功能，降低线粒体膜电位，并引发脂质过氧化和线粒体蛋白质和mtDNA的氧化损伤。在过去的20年中，已经合成了许多不同结构的针对线粒体的抗氧化剂（mito-AOX），这些抗氧化剂可以在线粒体内积累并清除自由基。在多种常见疾病和病理状态下，已经证明了它们基于预防氧化应激和恢复线粒体功能的保护作用。本文回顾了有关体内或体外实验中不同mito-AOX在动物内毒素血症模型中有益应用的最新数据。在我们的综述中提出的结果证明了基于mito-AOX的方法在开发针对革兰氏阴性感染和LPS本身的新治疗策略方面的潜在潜力。本文回顾了有关体内或体外实验中不同mito-AOX在动物内毒素血症模型中有益应用的最新数据。在我们的综述中提出的结果证明了基于mito-AOX的方法在开发针对革兰氏阴性感染和LPS本身的新治疗策略方面的潜在潜力。本文回顾了有关体内或体外实验中不同mito-AOX在动物内毒素血症模型中有益应用的最新数据。在我们的综述中提出的结果证明了基于mito-AOX的方法在开发针对革兰氏阴性感染和LPS本身的新治疗策略方面的潜在潜力。