Oxygen toxicity

Oxidative stress and cell proliferation 3.1. Oxygen toxicity 

Despite the central role of oxygen in the synthesis of ATP via oxidative phosphorylation it is now clear that oxygen can have inhibitory effects on the proliferation of cultured mammalian cells. For example, as oxygen concentrations are raised, cultured human fibroblasts begin to manifest reduced proliferation which results from an increase in non-cycling cells [22]. 

Excess superoxide on the other hand could interact with protons within membranes with the resultant generation of hydroperoxyl radicals (HOj) which, in principle, could also initiate lipid peroxidation [19]. Despite these routes to injurious free radical attack, for example following hyperoxic exposure, cell membranes can nevertheless in principle be protected by a-tocopherol, the major lipid-soluble chain-breaking antioxidant [19], A potential problem exists however when available o-tocopherol is limited, as lipid peroxides can break down to yield potentially toxic aldehydic products such as 4-hydroxynonenal. However in principle again these can be detoxified by the 

There have been a number of observations that indicate an apparent inverse relationship between levels of cellular lipid peroxidation and rates of cell proliferation [32,33] and extent of differentiation. Moreover in regenerating rat liver the periodic bursts of DNA synthesis (S-phases) are linked to corresponding depressions in the susceptibility of membranes to lipid peroxidation [34]. In addition, levels of a-tocopherol rise in relation to these periods of DNA synthesis (S-phases) [34], 

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SUPEROXIDE DISMUTASE PROTECTS AEROBIC ORGANISMS AGAINST OXYGEN TOXICITY... 

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

Pulmonary Oxygen Toxicity Radiation Pneumonitis "Shock Lung"... 

Ferrari, R., Ceconi, C., Curello, S., Guamieri, C., Caldarera, C., Albertini, A. and Visioli, O. (1985). Oxygen-mediated myocardial damage during ischaemia and reperfusion role of the cellular defences against oxygen toxicity. J. Mol. Cell. Cardiol. 17, 937-945. 

Halliwell, B. and Gutteridge, J.M.C. (1984). Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219, 1-14. 

As soon as it was appreciated that oxygen toxicity was somehow involved in retrolental fibroplasia, antioxidant administration was empirically investigated in both animal models and babies. In 1949, Owens and Owens reported a protective effect of vitamin E unfortunately this could not be substantiated in subsequent controlled trials. Phelps and Rosenbaum (1977) investigated whether vitamin E supplementation would influence oxygen-induced retinopathy in kittens and found it to be beneficial in reducing the severity of the lesions. Nevertheless, vitamin E has not yet been used with much success in preterm babies. 

Tripathi, B. and Tripathi, R. (1984). Cellular and subcellular events in retinopathy of oxygen toxicity with a preliminary report on the preventative role of vitamin E and gamma-aminobutyric acid a study in vitro. Curr. Eye Res. 3, 193-208. 

Forman, H.J., Rotman, E.I. and Fisher, A.B. (1983). Roles of selenium and sulfur-containing amino acids in protection against oxygen toxicity. Lab. Invest. 49, 148-153. 

Elevation of lung gjutathione by oral supplementation of L-2-oxathiazolidine-4-carboxylate protects against oxygen toxicity in protein-energy malnourished rats. FASEB J. 6, 3101-3107. 

Selenium is required, but levels must fall into a narrow window. Both deficiency and toxicity symptoms occur. The element is also used therapeutically in cancer treatment. It is the co-factor of the enzyme glutathione peroxidase which is thought to play an important role in oxygen toxicity. The determination of Se in blood or serum is not easy, as many incorrect, inaccurate and imprecise methods have been published (Magee and James 1994). A suggested procedure for Se in body fluids is based on GF-AAS (Thomassen et al. 1994)- For tissues SS-AAS may be used (Fler-ber 1994a). Recent developments by Turner et al. (1999) show that LC-ICP-MS is sensitive and reproducible at low levels. 

Talalay, P., A. T. Dinkova-Kostova, and W. D. Holtzclaw. 2003. Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. Adv Enzyme Regul 43 121-134. 

Ferrous iron, by its reaction with hydrogen peroxide in the Fenton reaction, can yield the toxic hydroxyl radical, OH, which will further potentiate oxygen toxicity. 

Vilim V, Nerudova J, Frantik E, et al. 1988. Acrylonitrile potentiation of oxygen toxicity in rats. Biomed Biochim Acta 47 206-209. 

Thrombolytic agent Thrombolytic agent Anticoagulant Haemophilia B Anti-cancer agent Cystic fibrosis Gaucher s disease Fabry disease Hyperuricaemia Mucopolysaccharidosis Oxygen toxicity Pompe disease... 

AMORY, A.M, FORD, L., PAMMENTER, N.W., CRESSWELL, C.F., The use of 3-amino-1,2,4-triazole to investigate the short-term effects of oxygen toxicity on carbon assimilation by Pisum sativum seedlings, Plant Cell Env., 1992,15,655-663. 

The O2 molecule is essential to all aerobic forms of life, but many anaerobic organisms (e.g. anaerobic bacteria such as Clostridia spp.) are killed after only brief exposures to molecular O2. However, it is well established that even aerobic organisms, including man and other animals, show signs of oxygen toxicity when exposed to O2 tensions above those normally found in air (i.e. >21% O2). Such toxicity does not normally occur because aerobic cells possess protective enzymes that prevent either the formation or the accumulation of oxygen metabolites. It is only when these protective systems be-... 

Fridovich, I. (1978). The biology of oxygen radicals The superoxide radical is an agent of oxygen toxicity superoxide dismutases provide an important defence. Science 201, 875-80. 

Another example of a diving problem that is a direct consequence of Dalton s Law of partial pressure concerns oxygen toxicity. The deeper a diver descends, the greater the partial pressure of oxygen. At a depth of 130 feet, the total pressure is close to 5 atmospheres and the partial pressure of oxygen will be close to 1 atmosphere (21% X 5 atmospheres). What this means is that breathing compressed air at 130 feet is like... 

The relationship between EC-SOD expression and NO production in cells is of a great physiological and pathophysiological significance. In 1992, Oury et al. [35] demonstrated that EC-SOD increased oxygen toxicity in central nervous system (CNS) by the inhibition of superoxide-mediated inactivation of nitric oxide. This conclusion is obviously erroneous one because, as it is well known that the interaction of superoxide and nitric oxide results in the formation of a very toxic peroxynitrite. Indeed, the same authors recently showed that EC-SOD promoted nitric oxide vasodilation by dismuting superoxide [36]. On the other hand, it has been found that nitric oxide can downregulate the synthesis of EC-SOD by smooth muscle cells [37]. 

Superoxide dismutases together with catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1,11.1.9) are important enzymes for the protection against oxygen toxicity 1.197-199) Protection is also provided by substances like a-tocopherol (vitamin E)... 

Fee, J. A. Superoxide, superoxide dismutases, and oxygen toxicity. In Metal Ion Activation of Dioxygen (Spiro, T. G, ed.). New York-Chichester-Brisbane-Toronto, Wiley-Interscience, 1980, pp. 209-237... 

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... 

Oshino, N, Chance, B. A survey of factors involved in cellular oxygen toxicity. In Biochemical and Medical Aspects of Active Oxygen (Hayaishi, O.. Asada, K., eds.), Baltimore-London-Tokyo, University Park Press, 1977, pp. 191-207... 

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