Free radical superoxide production

Teleost hsh, unlike any other known vertebrate group, contain multiple forms of the C3a anaphylatoxin as a result of the multiple isoforms of C3. All of these molecules are functionally active and play a prominent role in inducing oxygen free radical (superoxide) production from fish leucocytes. The C5a anaphylatoxin has also been characterized in fish, and as in mammals plays an important role in leucocyte chemotaxis and in triggering the respiratory burst of leucocytes (Sunyer et al., 2005). Interestingly, it has been shown that rainbow trout anaphylatoxins play an unexpected role in enhancing phagocytosis of particles (Li et al., 2004). 

Not all oxidants formed biolc cally have the potential to promote lipid peroxidation. The free radicals superoxide and nitric oxide [or endothelium-derived relaxing aor (EDRF)] are known to be formed in ww but are not able to initiate the peroxidation of lipids (Moncada et tU., 1991). The protonated form of the superoxide radical, the hydroperoxy radical, is capable of initiating lipid peroxidation but its low pili of 4.5 effectively precludes a major contribution under most physiological conditions, although this has been suggested (Aikens and Dix, 1991). Interestingly, the reaction product between nitric oxide and superoxide forms the powerful oxidant peroxynitrite (Equation 2.6) at a rate that is essentially difiiision controlled (Beckman eta/., 1990 Huie and Padmaja, 1993). 

Kinins, neuropeptides, and histamine are also released at the site of tissue injury, as are complement components, cytokines, and other products of leukocytes and platelets. Stimulation of the neutrophil membranes produces oxygen-derived free radicals. Superoxide anion is formed by the reduction of molecular oxygen, which may stimulate the production of other reactive molecules such as hydrogen peroxide and hydroxyl radicals. The interaction of these substances with arachidonic acid results in the generation of chemotactic substances, thus perpetuating the inflammatory process. 

Oxidative stress and free-radicals The production of free-radicals and other reactive species has been much implicated in cytotoxicity. This topic is discussed in more detail elsewhere see ANTIOXIDANTS PREE-RADICAL SCAVENGERS nitric oxide synthase inhibitors. The production of these species in oxidative stress is well established. Advances in therapy may well be in the direction of boosting and augmenting natural defence processes, for example, by superoxide dismutase (SOD), catalase, a-tocopherol, glutathione, ascorbic acid and perhaps melatonin. Surprisingly, some forms of the enzyme SOD can be administered in vivo and are protective. 

Allopurinol, which inhibits XO and scavenges superoxide, prevents the increase in free-radical production... 

It has already been stressed that the discovery of superoxide as the enzymatically produced diffusion-free dioxygen radical anion [1-3] was a pivotal event in the study of free radical processes in biology. It is not of course that the McCord and Fridovich works were the first ones in free radical biology, but the previous works were more of hypothetical character, and only after the identification of superoxide by physicochemical, spectral, and biochemical analytical methods the enzymatic superoxide production became a proven fact. 

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