Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs preconditioning

Abstract

Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear. However, an emerging body of evidence indicates that the generation of reactive oxygen species (ROS) by mitochondria plays a critical role in damaging cellular components and initiating cell death. In this review, we summarize our current understanding of the mechanisms whereby mitochondrial ROS generation occurs in I/R and contributes to myocardial infarction and stroke. In addition, mitochondrial ROS have been shown to participate in preconditioning by several pharmacologic agents that target potassium channels (e.g., ATP-sensitive potassium (mKATP) channels or large conductance, calcium-activated potassium (mBKCa) channels) to activate cell survival programs that render tissues and organs more resistant to the deleterious effects of I/R. Finally, we review novel therapeutic approaches that selectively target mROS production to reduce postischemic tissue injury, which may prove efficacious in limiting myocardial dysfunction and infarction and abrogating neurocognitive deficits and neuronal cell death in stroke.

Insights into the Pathogenic Secondary Symptoms Caused by the Primary Loss of Dystrophin

“…Elevated intracellular concentration of Ca 2+ can alter mitochondria permeability and function, thereby inducing degenerative pathways and ROS production [86,[91][92][93][94]. Reactive oxygen molecules, in turn, are able to react with fatty acids inducing lipid peroxidation, resulting in membrane insult [95].…”

Oxidative stress in severe pulmonary trauma in critical ill patients. Antioxidant therapy in patients with multiple trauma — a review

“…Reactive oxygen species are produced in high quantities through endogenous metabolisms [27], while at the same time, there are also a large class of exogenous factors that increase the production of free radicals. Such mechanisms that can generate free radicals inside the body are represented by: the activation of neutrophils, the electron transport chain at the mitochondrial level, arachidonic acid metabolism, oxide-reduction of xanthine [28] or nitric oxide synthesis [27,[29][30][31].…”

“…Such mechanisms that can generate free radicals inside the body are represented by: the activation of neutrophils, the electron transport chain at the mitochondrial level, arachidonic acid metabolism, oxide-reduction of xanthine [28] or nitric oxide synthesis [27,[29][30][31]. The respiratory chain [32][33][34] has a key role at the cellular level, being responsible for the conversion of oxygen in water molecules.…”

Cardioprotective Effect of Inm 176 on Ischemia Reperfusion Injury Using Rat Heart Model

“…Ischemia accompanied by reperfusion can result into reversible or irreversible myocardial injury; however, it also depends on its duration as well as on severity [2]. If reperfusion does not occur, then ischemia leads to cell death.…”