Abstract:

Ischemia-reperfusion damage causes high morbidity and mortality for patients who have clinical conditions such as myocardial infarction, organ transplantations, cerebrovascular infarction, cardiopulmonary resuscitation, thrombolytic therapy and hemorrhagic shock. Ischemic tissue damage starting with decreasing blood supply and oxygen deficiency in affected tissues increases through reoxygenation when reperfusion provided. Decreasing mitochondrial ATP production causes shift from aerobic to anaerobic intracellular metabolism and leads to acidosis. Decelerating of ATP dependent Na-K pumps leads to increased intracellular hydrogen load. This increase in hydrogen ions is balanced with increased intracellular calcium levels via Na-Ca pumps. Increased calcium ions also activate many cytosolic proteases. Tissue reoxygenation with reperfusion accelerates several critical biochemical pathways for the production of reactive oxygen species (ROS) such as hydroxyl radicals (OH•), superoxide radicals (O2•-) and hydrogen peroxides H2O2 and reactive nitrogen species (RNS) such as peroxynitrides (ONOO-). However, increased reactive radicals can lead to collection of inflammatory cells to the inflammatory region. Cytokines released through the interaction between inflammatory (especially polymorphonuclear leukocytes) and endothelial cells cause expanding of damage due to reperfusion. Xanthine oxidase, nitric oxide synthase, NADPH oxidase, which is responsible for respiratory burst in phagocytes, and electron transport chain in mitochondria are the main mechanisms responsible for the production of ROS and RNS. These free radicals attack important macromolecules such as lipid structures of cell membranes, intracellular proteins and genetic material and can cause cell damage and death. Since ischemiareperfusion injury is a quite complex process, the relationship between ischemia-reperfusion and oxidative stress mainly discussed in this review

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