Oxidative Stress

Several lines of evidence suggest that oxidatively modified LDL plays an important role in the development of atherosclerosis. Oxidative modification of LDL involves peroxidation of PUFAs. LDL particles enriched in PUFAs have been shown to be more susceptive to oxidative modification compared to LDL particles rich in monounsaturated fatty acids. Others have also suggested that a diet high in PUFAs may overwhelm the antioxidant defenses of cells. In particular, studies have shown that LA-enriched LDL is more prone to in vitro oxidation than oleic acid-enriched LDL. Concern also remains with respect to the potential for increased lipid peroxidation following n-3 fatty acids. To date, however, the data in vivo are inconclusive, with observations of increased, unchanged, and decreased lipid peroxidation. The most plausible explanation relates to differences in the methodologies employed to assess lipid peroxidation. Much of the literature relating to PUFAs and lipid peroxidation is based on indirect and nonspecific assays, including measurement of LDL oxidative susceptibility, which relies on the isolation of LDL from plasma. In this regard, the recent discovery of F2-isoprostanes, which are non-enzymatic prostaglandin-like products of free radical peroxidation of arachidonic acid, has allowed for the direct assessment of in vivo lipid peroxidation. There is now good evidence that quantitation of F2-isoprostanes provides a reliable measure of in vivo oxidative stress. Using measurement of F2-isoprostanes, recent data have demonstrated that n-3 fatty acids decrease oxidative stress. It has also been suggested that the concentration of PUFAs may be a more important factor affecting lipid peroxidation than the degree of unsaturation. Further research using better markers of lipid peroxidation is required before definitive statements can be made relating to the effect of n-6 fatty acids, and indeed PUFAs in general, on oxidative stress.

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