Mechanisms of Cell Injury by Activated Oxygen Species

Abstract

Current evidence suggests that O2 and H2O2 injure cells as a result of the generation of a more potent oxidizing species.In addition to O2 and H2O2 the third essential component of the complex that mediates the lethal cell injury is a cellular source of ferric iron.The hypothesis most consistent with all the available data suggests that O2 reduces a cellular source of ferric to ferrous iron, and the latter then reacts with H2O2 to produce a more potent oxidizing species, like the *OH or an equivalently reactive species.In turn, *OH initiates the peroxidative decomposition of the phospholipids of cellular membranes."OH also damages the inner mitochondrial membrane.Upon mitochondrial deenergization, a sequence of events is initiated that similarly leads to the loss of viability of the cell.DNA represents a third cellular target of *OH.Depending on the cell type, oxidative DNA dam- age can be coupled to cell killing through a mechanism related to the activation of poly (ADP-ribose) polymerase.-