The role of oxygen radicals in human disease, with particular reference to the vascular system.

Free radicals, such as superoxide, hydroxyl and nitric oxide, and other reactive oxygen species (ROS), such as hydrogen peroxide, are formed in vivo. Imbalance between production of ROS and anti-oxidant defence can result in oxidative stress, which may arise either from deficiencies of anti-oxidants (such as glutathione, ascorbate or alpha-tocopherol) and/or from increased formation of ROS. Oxidative stress can result in glutathione depletion, lipid peroxidation, membrane damage and DNA strand breaks as well as activation of proteases, nucleases and protein kinases. Some degree of oxidative stress occurs in most, if not all, human diseases, and the major question to be answered is whether it makes a significant contribution to the disease pathology. In the case of atherosclerosis, evidence from studies with the chain-breaking anti-oxidant probucol and from epidemiological work suggests that oxidative damage does indeed make an important contribution to plaque development.