Free radical oxygen toxicity

In these reactions that mediate the nucleic acid cleavage reactions by generation of reactive oxygen species (ROS), unwanted side effects such as lipid peroxidation and free radical induced toxicity may limit their use as has been postulated in case of Fe +/ +-gentamicin complexes. ... 

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... 

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

Hull, D.S. and Green, K. (1989). Oxygen free radicals and corneal endothelium. Lens Eye Toxic Res. 6, 89-91. 

Mossman, B.T. and Marsh, J.P. (1985). Mechanisms of cell toxic injury by asbestos fibres role of oxygen free radicals. In In vitro Effects of Mineral Dusts (eds. E.G. Beck and J. Bignon) pp. 66-81. Springer Verlag, Berlin. 

Iron is an extremely important element present in all living organisms correspondingly, iron metabolism is well studied. Both iron deficiency and iron excess are origins of serious pathologies (iron-deficit anemias, hereditary hemochromatosis, thalassemia, etc.) associated with the overproduction of oxygen radicals. Free radical-mediated processes, characteristic of these pathologies, are considered in Chapter 31 here we will look at some mechanisms of toxic effects of iron. 

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). 

A one-electron reduction of the bond between an aliphatic carbon and a halogen leads to a halogen anion and a carbon-free radical. A good example is the reduction of carbon tetrachloride as discussed earlier in this chapter. The first product in the reduction is the trichloromethyl-free radical. Carbon-centered radicals are not very reactive with biological molecules, but they react very rapidly with molecular oxygen (a diradical) to form a peroxy-free radical (Fig. 5.15), which is quite toxic (10). 

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