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
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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.