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Superoxide dismutase (SOD)

Superoxide dismutase (SOD) is the enzyme that catalyzes the removal of superoxide radicals, which are generated in a variety of biological oxidations. Superoxide is a highly oxidative species present in disease states, which reacts with endogenous nitric oxide (NO) to produce the oxidative species peroxynitrite, a cell damaging oxidative species which also causes lipid peroxidation. Moreover, superoxide consequently lowers the endogenous nitric oxide concentration. Endogenous nitric oxide has a number of beneficial effects, and one aspect of the invention is a method of preventing or inhibiting the removal of endogenous nitric oxide by superoxide, to, for example, prevent or inhibit restenosis, and to stabilize a vulnerable plaque from erosion and/or rupture and thrombosis. Active oxygen species are involved in the pathogenesis of a variety of diseases. Accumulation of active oxygen species, and oxygen-free radicals, as well as direct oxygen toxicity can cause oxidative damage to cells. Oxidative damage can occur in various lung diseases, cancer and inflammatory diseases, and in other conditions involving hypoxia or ischemia-reperfusion injury, such as organ transplantation. Superoxide radicals are extremely reactive intermediate forms of the natural oxygen molecule and, as a result of this property, can irreversibly damage organic compounds in the cells of the human body. As protection from the dangerous effect of these superoxide radicals, the cells have an enzyme which is capable of rapidly converting such superoxide radicals into the more rapidly metabolizable and less toxic hydrogen peroxide. The superoxide dismutases are characterized in families based on the metal ion associated with the enzyme, where the ions can be iron, manganese, copper, and copper and zinc. Superoxide dismutase catalyzes the conversion of superoxide radicals into molecular oxygen and hydrogen peroxide. The conversion of superoxide radicals is generally beneficial to a cell, since such molecules can react with the cell's genomic DNA to induce mutations. It provides a defense against oxygen toxicity and damage than may be caused to cells by carcinogenic hydrocarbons (1). The human Cu--Zn superoxide dismutase (SOD-1) is a dimeric protein composed of apparently identical noncovalently linked subunits, each with a molecular weight of 16,000-19,000 (2,3). The locus for human cytoplasmic superoxide dismutase (SOD-1) was assigned to chromosome 21. Superoxide dismutase, e.g., from bovine liver, has found clinical use, particularly as an anti-inflammatory agent in mammals including humans and to decrease tissue injury due to reperfusion (post-ischemic). Other uses include scavenging superoxide anions due to exposure of a host to various superoxide-inducing agents, e.g. radiation, paraquat, etc.; prophylaxis or therapy for certain degenerative diseases, e.g., emphysema; food preservation. Superoxide dismutases (SOD) have been classified based on the inorganic atoms they require for activity. Three SOD families have been identified: those requiring manganese (MnSOD), those requiring iron (FeSOD), and those requiring copper and zinc (Cu, ZnSOD).

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