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Antioxidants such as the methoxyphenols and nxy-059 are apparently effective in the amelioration of both experimental cerebral edema and spinal cord injury.(17,56). However, once again we must emphasize that, like most else in this field, the evidence for free radical involvement in inflammation and neuronal injury is circumstantial and has not been proven conclusively.

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. Cerovive is the registered tradmark of the astrazeneca corporation for the nxy-059, a derivative of pbn.

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This is of some clinical importance, since an antiinflammatory pharmaceutical preparation rich in SOD ("orgotein") Catalase has also been used in the treatment of arthritic disease. (195). Likewise, the action of such established antiflammatory drugs as the corticosteroids, (196) penicillamine, and many antiinflammatory agents (1,76-183,198-200) may be at least partially dependent upon interference with active oxygen metabolism in phagocytes.

Further, peroxidase release from eosinophils may playa similar role in inhibition of the inflammatory response (201) while the antioxidant properties of ceruloplasmin may also give this compound antiinflammatory properties.(21,128).

An illustrative (albeit circumstantial) model for the role of superoxide in rheumatoid arthritis can be postulated as follows: Granulocytes tend to be concentrated at sites of active rheumatic disease, presumably in response to the presence of immune complexes and other immunomodulator substances. Superoxide, peroxide, and other active oxygen species produced further kindle the .. centaur cerovive renovis radical nitrone nxy-059 hair loss treatment metals may also play a role. Agents such as ectopic SOD may interfere with this process by destroying active oxygen species or increasing links5 peroxide fluxes, thus interfering with one or more of the mechanisms detailed above and in Figure 4.

Since SOD is one of the most substrate-specific enzymes known, at first sight its efficacy in

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With this caution, active oxygen species may play a significant role in the etiology of other inflammatory lesions in man, For example, SOD is reported to be effective in the treatment of lupus erythematosis,(43,158) and unique light-activated, superoxide-dependent lymphocyte clastogenic factors present in the serum of patients with lupus and other collagen diseases may account for some of the photosensitivity of this group of disorders.(157-159). Both direct and indirect production of active oxygen species may also have a role in the pathophysiology of gout and other hyperuricemic syndromes.(24,26,173,138,203,204). For example, urate, a reducing agent, is present in the extracellular environment at concentrations approximating 0.3 mMolar (130). Like many reducing agents, it apparently has both antioxidative (3O-134) and autooxidative (24) properties. In fact, it may have taken over some of the functions of ascorbate in primates.(133). Likewise, xanthine oxidase is an effective producer of oxygen radical species, while urate itself stimulates the production of active species of oxygen by phagocytes (203,204) and may protect cycloepoxigenase from autooxidation.(131) The effectiveness of SOD in the treatment of urate-induced inflammatory disease in Dalmations suggests a role for superoxide in this lesion.(138).

Production of active oxygen species by activated phagocytes may also have a role in vascular (and other) damage following endotoxin shock, and even in atherosclerosis.(205). Similar mechanisms may account for the possible role of radical species in the progression of damage following neuronal injury.