Free Radicals, Types, Sources and Damaging Reactions
Submitted by Dr. Tamer Fouad, M.D.
Free radicals are a chemical species that possess an unpaired electron in the outer shell of the molecule.
Sources of Free Radicals (continued)
A number of drugs can increase the production of free radicals in the presence of increased oxygen tensions. The agents appear to act additively with hyperoxia to accelerate the rate of damage. These drugs include antibiotics that depend on quinoid groups or bound metals for activity (nitrofurantoin), antineoplastic agents as bleomycin, anthracyclines (adriamycin) (Fisher, 1988) and methotrexate, which possess pro-oxidant activity (Gressier et al. 1994). In addition radicals derived from penicillamine, phenylbutazone, some fenamic acids and the aminosalicylate component of sulphasalazine might inactivate protease and deplete ascorbic acid accelerating lipid peroxidation (Grisham et al. 1992; Halliwel et al. 1992a; Evans et al. 1994).
Radiotherapy may cause tissue injury that is caused by free radicals. Electromagnetic radiation (X rays, gamma rays) and particulate radiation (electrons, photons, neutrons, alpha and beta particles) generate primary radicals by transferring their energy to cellular components such as water. These primary radicals can undergo secondary reactions with dissolved oxygen or with cellular solutes.
Oxidants in tobacco exist in sufficient amounts to suggest that they play a major role in injuring the respiratory tract. It has been shown that tobacco smoke oxidants severely deplete intracellular antioxidants in the lung cells in vivo by a mechanism that is related to oxidant stress. It has been estimated that each puff of smoke has an enormous amount of oxidant materials. These include aldehydes, epoxides, peroxides, and other free radicals that may be sufficiently long lived as to survive till they cause damage to the alveoli. In addition nitric oxide, peroxyl radicals and carbon centred radicals are present in the gas phase. In addition it also contains other relatively stable radicals in the tar phase. Examples of radicals in the tar phase include the semiquinone moieties derived from various quinones and hydroquinones. Again micro-haemorrhages are most probably the cause of iron deposition found in smokers' lung tissue. Iron in this form leads to the formation of the lethal hydroxyl radical from hydrogen peroxide. It was also found that smokers have elevated amounts of neutrophils in the lower respiratory tract that could contribute to a further elevation of the concentration of free radicals.
Inhalation of inorganic particles also known as mineral dust (e.g. asbestos, quartz, silica) can lead to lung injury that seems at least in part to be mediated by free radical production. Asbestos inhalation has been linked to an increased risk of developing pulmonary fibrosis (asbestosis), mesothelioma and bronchogenic carcinoma. Silica particles as well as asbestos are phagocytosed by pulmonary macrophages. These cells then rupture, releasing proteolytic enzymes and chemotactic mediators causing infiltration by other cells such as neutrophils, thus initiating an inflammatory process (Kehrer JP, Mossman BT, Sevanian A, Trush MA, Smith MT; 1988), that leads to increased production of free radicals and other reactive oxygen species (Heffner and Repine, 1989; Vallyathan et al. 1988). Furthermore, asbestos fibres contain iron, which may have been derived form haemoglobin liberated from micro-haemorrhages. This iron can stimulate the formation of hydroxyl radicals.
Ozone is not a free radical but a very powerful oxidising agent. Ozone (O3) contains two unpaired electrons and degrades under physiological conditions to ?OH, suggesting that free radicals are formed when ozone reacts with biological substrates. In support of this hypothesis, ozone can generate lipid peroxidation in-vitro, although similar findings in-vivo have not been demonstrated.
Fever, excess glucocorticoid therapy and hyperthyroidism decrease oxygen tolerance in experimental animals. The decrease is attributable to the increased generation of oxygen-derived radicals that accompanies increased metabolism. In addition, a wide variety of environmental agents including photochemical air pollutants as pesticides, solvents, anaesthetics, exhaust fumes and the general class of aromatic hydrocarbons, also cause free radical damage to cells.
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