Biochemical aspects of free radicals metabolism

The lung is particularly exposed to oxidant stresses, such as those that can be brought about by oxygen-derived free radicals. They mainly result from the monovalent reduction of molecular oxygen. The most reactive oxygen metabolite is the hydroxyl radical, whose formation appears to be dependent upon the presence of iron-chelates. Free radicals are normally produced by cellular metabolism. Furthermore, activated phagocytes, during the 'respiratory burst', release oxygen metabolites that are necessary for bacterial killing. Free radicals are highly reactive species. Their target molecules are proteins, DNA and polyunsaturated fatty acids whose alterations can lead to cell death. There are, however, several antioxidant substances which are enzymatic (superoxide dismutases, catalase and glutathione peroxidase) and non enzymatic (reduced glutathione, vitamin E and C etc...). In many experimental systems, an increase in antioxidant defences is associated with higher resistance to oxidant stress. However, the antioxidant system may be overwhelmed by an overproduction of intra and/or extracellular free radicals leading to tissue injury. Recent advances in the understanding of free radical metabolism can suggest some new therapeutic approaches such as the administration of exogenous antioxidant or iron chelators.