MECHANISMS OF CELL INJURY BY ACTIVATED OXYGEN SPECIES

Current evidence suggests that O-2(-) and H2O2 injure cells as a result of the generation of a more potent oxidizing species. In addition to O-2(-) 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 O-2(-) reduces a cellular source oi ferric to ferrous iron, and the latter then reacts with H2O2 to produce a more potent oxidizing species, like the (OH)-O-. or an equivalently reactive species. In turn, (OH)-O-. initiates the peroxidative decomposition of the phospholipids of cellular membranes. (OH)-O-. 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)-O-.. Depending on the cell type, oxidative DNA damage can be coupled to cell killing through a mechanism related to the activation of poly (ADP-ribose) polymerase.