Oxygen radicals: mediators of gastrointestinal pathophysiology.

Oxygen radicals: mediators of gastrointestinal pathophysiologyRecent evidence suggests that reactive oxygen metabolites are mediators of the microvascular and parenchymal cell injury associated with ischaemia and subsequent reperfusion.Under normal conditions, approximately 95% of molecular oxygen in biological systems undergoes controlled reduction through the addition of four electrons (tetravalent) in the mitochondrial cytochrome oxidase system to form water. ' The remaining molecular oxygen undergoes sequential, univalent reduction to produce the partially reduced oxygen free radical intermediates, superoxide anion (02-), hydrogen peroxide (H202) and the highly reactive hydroxyl radical (OH).Nature has provided a myriad of antioxidant enzymes and scavengers to protect against the deleterious effects of these highly reactive metabolites of oxygen.The primary defence against oxidative insults to the tissue include the enzymes, superoxide dismutase, catalase, and glutathione peroxidase.Superoxide dismutases are a family of predominantly intracellular metallo- proteins that catalyse dismutation of 02to H202.Only trace amounts of superoxide dismutase activity are detected in extracellular fluid -that is, plasma, spinal fluid and lymph.2Two enzyme systems are important in regulating the intracellular concentration of H202.Catalase is a haemo- protein which catalyses decomposition of H202 to water.Glutathione peroxidase is a cytoplasmic, selenium containing enzyme which catalyses decomposition of H202 or organic peroxides to water or the corresponding organic alcohol.The antioxidant activity of glutathione peroxidase is coupled to the oxidation of reduced glutathione to oxidised glutathione which can be subsequently reduced by glutathione reductase using NADPH as the reducing agent.A selenium independent form of glutathione peroxidase has recently been described.'In addition to antioxidant enzymes, a multitude of water soluble -for example, ascorbic acid, cysteine, and lipid solublefor example, a-tocopherol, ,6-carotene, antioxidants provide a second line of defence against oxidant induced tissue injury. Sources of oxygen radicalsOxygen free radicals may be formed from several sources, including: components of the mitochondrial electron transport system; endoplasmic reticulum; prostaglandin synthetase and lipoxygenase systems; soluble enzymes and proteins; and autoxidation of several compounds and xeno- biotics.Of the multitude of potential sources of reactive oxygen metabolites, two major enzymes have been implicated in the tissue damage associated with ischaemia reperfusion, xanthine oxidase, and neutrophilic NADPH oxidase.