Stepien Karolina M, Heaton Robert, Rankin Scott, Murphy Alex, Bentley James, Sexton Darren, Hargreaves Iain P
The Mark Holland Metabolic Unit Salford Royal NHS Foundation Trust Stott Lane, Salford M6 8HD, UK.
School of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UK.
J Clin Med. 2017 Jul 19;6(7):71. doi: 10.3390/jcm6070071.
Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of a number of diseases and conditions. Oxidative stress occurs once the antioxidant defenses of the body become overwhelmed and are no longer able to detoxify reactive oxygen species (ROS). The ROS can then go unchallenged and are able to cause oxidative damage to cellular lipids, DNA and proteins, which will eventually result in cellular and organ dysfunction. Although not always the primary cause of disease, mitochondrial dysfunction as a secondary consequence disease of pathophysiology can result in increased ROS generation together with an impairment in cellular energy status. Mitochondrial dysfunction may result from either free radical-induced oxidative damage or direct impairment by the toxic metabolites which accumulate in certain metabolic diseases. In view of the importance of cellular antioxidant status, a number of therapeutic strategies have been employed in disorders associated with oxidative stress with a view to neutralising the ROS and reactive nitrogen species implicated in disease pathophysiology. Although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical management of patients. The purpose of this review is to highlight the emerging evidence of oxidative stress, secondary mitochondrial dysfunction and antioxidant treatment efficacy in metabolic and non-metabolic diseases in which there is a current interest in these parameters.
线粒体功能障碍和氧化应激与多种疾病和病症的发病机制有关。一旦身体的抗氧化防御系统不堪重负，无法再对活性氧（ROS）进行解毒，氧化应激就会发生。然后ROS就会不受阻碍，能够对细胞脂质、DNA和蛋白质造成氧化损伤，最终导致细胞和器官功能障碍。虽然线粒体功能障碍并不总是疾病的主要原因，但作为病理生理学的继发性疾病，它可导致ROS生成增加以及细胞能量状态受损。线粒体功能障碍可能是由自由基诱导的氧化损伤或某些代谢疾病中积累的有毒代谢产物的直接损害引起的。鉴于细胞抗氧化状态的重要性，人们已经在与氧化应激相关的疾病中采用了多种治疗策略，以中和与疾病病理生理学相关的ROS和活性氮物质。尽管在某些情况下取得了成功，但这些辅助疗法尚未纳入患者的临床管理中。本综述的目的是强调在目前对这些参数有研究兴趣的代谢性和非代谢性疾病中，氧化应激、继发性线粒体功能障碍和抗氧化治疗效果的新证据。
