An approach to free radicals in medicine and biology.

Evolutionary pressure induced by the release of O2 into the environment has necessitated the development of a group of mechanisms to deal with the toxic free radical byproducts of oxidative metabolism. The complete reduction of O2 to H2O2 involves the addition of four electrons which can occur univalently resulting in a series of toxic intermediates or quadrivalently by the mitochondrial cytochrome oxidase system, which avoids these reactive intermediates. Free radical mechanisms have been associated with a large number of disease states including inflammation, irradiation-induced injury and ischemia. The site of free radical generation, that is whether the generation of radical species is predominantly extracellular or intracellular, may determine to a degree, the types of macromolecular and cellular damage which result. A classification of diseases in which radical generating processes may play a role is presented in the hope that it may aid in the understanding and treatment of these diseases.