Oxygen toxicity, superoxide free radical

Bannister, J, V., Hill, H. A. O. (eds.) Chemical and Biochemical Aspects of Superoxide and Superoxide Dismutase, New York-Amsterdam-Oxford, Elsevier/North-Holland, 1980, p. 414 Fridovich, I. Oxygen radicals, hydrogen peroxide, and oxygen toxicity. In Free Radicals in Biology, Vol. I (Pryor, W. A., ed.). New York-San Francisco-London, Academic Press, 1976, pp. 239-277... 

Tissues are protected from oxygen toxicity caused by the superoxide free radical by the specific enzyme superoxide dismutase. 

The toxic effects of oxygen can be attributed to its free radical activity. Biological oxidations and auto-oxidations can convert molecular oxygen to the free radical form, superoxide anion (O2 ). Other reactive intermediates include hydrogen peroxide (H2O2) and hydroxyl free radical (OH ). When these forms react with lipids, potent lipoperoxides form, which damage cell membranes and other vital cellular and subcel-lular structures [5]. 

One of the important consequences of neuronal stimulation is increased neuronal aerobic metabolism which produces reactive oxygen species (ROS). ROS can oxidize several biomoiecules (carbohydrates, DNA, lipids, and proteins). Thus, even oxygen, which is essential for aerobic life, may be potentially toxic to cells. Addition of one electron to molecular oxygen (O,) generates a free radical [O2)) the superoxide anion. This is converted through activation of an enzyme, superoxide dismurase, to hydrogen peroxide (H-iO,), which is, in turn, the source of the hydroxyl radical (OH). Usually catalase... 

Copper is part of several essential enzymes including tyrosinase (melanin production), dopamine beta-hydroxylase (catecholamine production), copper-zinc superoxide dismutase (free radical detoxification), and cytochrome oxidase and ceruloplasmin (iron conversion) (Aaseth and Norseth 1986). All terrestrial animals contain copper as a constituent of cytochrome c oxidase, monophenol oxidase, plasma monoamine oxidase, and copper protein complexes (Schroeder et al. 1966). Excess copper causes a variety of toxic effects, including altered permeability of cellular membranes. The primary target for free cupric ions in the cellular membranes are thiol groups that reduce cupric (Cu+2) to cuprous (Cu+1) upon simultaneous oxidation to disulfides in the membrane. Cuprous ions are reoxidized to Cu+2 in the presence of molecular oxygen molecular oxygen is thereby converted to the toxic superoxide radical O2, which induces lipoperoxidation (Aaseth and Norseth 1986). 

Nifurtimox (Lampit) is a nitrofuran derivative whose likely mechanism of action for kUhng of trypanosomes is through the production of activated forms of oxygen. Nifurtimox is reduced to the nitro anion radical, which reacts with oxygen to produce superoxide and hydrogen peroxide. The free radical metabolites, an absence of parasite catalase, and a peroxide dehciency lead to hpid peroxidation and cell damage. This production of activated oxygen results in toxicity to the protozoal cells. 

Although oxygen radicals are destructive to islet cells, the inability of nicotinamide, Probucol, and other free radical scavengers to completely prevent cytokine mediated islet destruction suggests that other cytotoxic mechanisms may be involved in cytokine-induced islet-cell lysis. The possible interactions of superoxide with nitric oxide resulting in the generation of peroxynitrite and hydroxyl radicals may contribute to islet-cell lysis. The chemistry of these free radical interactions, and potential biological roles t)f these toxic radicals are reviewed in this book (see Chapter 1). 

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