Production of free radicals in ischemiareperfusion

Free radicals are atomic or molecular structures with one or more unpaired electron in the outermost orbital. Such unpaired electrons make these species very unstable and therefore quite reactive: free radicals tend to react with other molecules to pair this electron and thereby generate a more stable species. Ground state molecular oxygen is a bioradical with its two outermost valance electrons occupying separate orbitals with parallel spins. Pairs of electrons typically have opposite spins, and thus fortunately impose a restriction on the reaction of molecular oxygen with most organic molecules. However, ground state oxygen may be converted to the much more reactive ROS (reactive oxygen species) forms by energy transfer (-> singlet oxygen) or by electron transfer reactions (superoxide, hydrogen peroxide and hydroxyl radical). The equilibrium between production and scavenging of ROS may be perturbed by a number of factors and disease states16'17. ROS recently have been related to signalling, and gene expression18. Free radical production is increased in ischemia-reperfusion syndromes (xanthine oxidase pathway and NADPH oxidase system), even though one would expect a reduced free radical production during times of hypoxia18'19. Reactive oxygen species generated during the reperfusion phase overwhelm the scavenging capacities of antioxidant enzymes, and result in oxidative damage.

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