ABSTRACT
Free radicals are atoms or molecules with an unpaired electron in the outer shell, and in complex molecules these may be centered on carbon, nitrogen, or oxygen. The definition of free radicals from a biologist's point of view is extended by defining a new category, reactive oxygen species (ROS), to include peroxides that are not radicals. However, peroxides can easily form them and playa central role in metabolism and inflammation. Thus this definition ofROS encompasses peroxides, which are radical precursors. The reason this chemistry is of interest to biologists is that the reactivity of radicals is high as they seek to pair with another atom and complete its own unfilled orbital. The free energy to be gained by this reaction means that many normally stable chemical bonds are susceptible to attack. The result is the facile addition of atoms and molecules to other molecules, or the rearrangement of the molecule that is exploited, for example, in the generation of the many leukotrienes, prostanoids, and thromboxanes that coordinate cellular actions in complex organisms. Radicals and reactive oxygen species are also used by the inflammatory cells of higher organisms to aid in the destruction of invading organisms, a mission that becomes apparent in chronic granulomatous disease where the ability of inflammatory cells to generate reactive oxygen species on demand is lost. Oxidants (in a currently undefined fashion) also regulate gene transcription through modulation of intracellular signal pathways leading to the activation of the transcription factors NF-kB (I) and AP-I (2). Oxidants also alter vascular tone, acting both as vasoconstrictors and vasodilators, so their final effect is variable (3). Free radicals, oxidants, and reactive oxygen species play diverse roles in metabolism, but by their very nature are able to cause inappropriate responses and widespread destruction. This capacity for mayhem is checked by mobile antioxidants, as well as dedicated intracellular and extracellular catabolic pathways. It is when this suppressive ability is overcome, even when the loss of control is only local, that a number of unintended events relevant to vascular biology become manifest. One of these consequences we know the most about is reviewed here: mimicry of physiological inflammatory processes.
