Free radical-lipid interactions and their pathological consequences.

ABSTRACT

In this review we have tried to present the current thinking on the consequences for lipids of their interactions with free radicals and the pathological implications. In particular, atherosclerosis and cancer have been addressed. In the case of the former, it is not clear whether the initial oxidative event is an enzymic or free radical-mediated process as yet. However, the importance of the antioxidants in controlling LDL oxidation, macrophage uptake of oxidatively modified LDL and progression of atheroma in animal models certainly suggests an important propagative role for free radical-mediated events. With regard to cancer, oxidative modification of cell lipids has potential consequences for tumour cell proliferation. Whilst lipid hydroperoxides can serve as an origin of prostaglandins with tumour inhibitor (or immunosuppressive) properties, they may also influence cellular growth regulatory proteins normally dependent on membrane lipid integrity. Alternatively, they may function as a source of aldehydic breakdown products capable of 'down-regulating' cell proliferation through covalent modification of regulatory proteins. Oils rich in n-3 polyunsaturated fatty acids have toxic effects towards tumour cells. This toxicity is not mediated by prostaglandins but rather through the capacity of such agents to elevate the levels of lipid peroxides. This may be enhanced by active oxygen species released constitutively from tumour cells.