The role of free radicals in liver damage.

Increasing evidence has accumulated over the last few years on the involvement of free radical reactions in the genesis of the liver cell damage which characterizes several pathological conditions. Such conditions can be classified as ( I ) toxic liver damage, (2) iron overload, (3) dietary deficiencies or imbalances. In the first case the active free radicals are generated during the metabolic attack of the poison in the smooth endoplasmic reticulum (SER) of the liver cell, and are chemically related to the poison itself. Such types of radicals are able to covalently bind to cell structures, with their consequent functional modification. Free radicals, however, are also able to abstract hydrogen from suitable substances, so producing their oxidation. If the oxidized substance is a polyunsaturated fatty acid, H abstraction usually starts a chain reaction called ‘lipid peroxidation’. This involves the production of lipid free radicals, as well as of other non-radical toxic products, especially carbonyls, that play an important role in cell damage. In the other two cases, i.e. Fe overload and dietary deficiencies or imbalances, oxygen free radicals may be involved, but lipid peroxidation is also important in the development of the damage. In the present paper, a critical reconsideration of the relative importance of the different free radical mechanisms in the production of the cell damage is attempted. Most of the attention is focused on the toxic forms of liver damage, where existing knowledge allows more definite conclusions.