The role of free radicals in toxicity and disease.

Free radicals are defined as atoms or molecules that contain one or more unpaired electrons. The toxicity of many xenobiotics is associated with the metabolic activation of foreign compounds to form free radicals or with the production of reactive oxygen species as superoxide anion, hydroxyl radicals or hydrogen peroxide which are responsible for the tissue damaging effects as lipid peroxidation, and DNA and protein damage. Oxidative stress associated with production of reactive oxygen species is believed to be involved not only in the toxicity of xenobiotics but also in the pathophysiology of aging, and various age-related diseases, including cataracts, atherosclerosis, neoplastic diseases, diabetes, diabetic retinopathy, chronic inflammatory diseases of the gastrointestinal tract, aging of skin, diseases associated with cartilage, Alzheimer's disease, and other neurologic disorders. The cellular sources of free radicals and reactive oxygen species, the biological targets of free radicals, and clinical conditions which are associated with free radical production and tissue damage are reviewed. In addition, potential therapeutic approaches to the prevention of free radical damage are considered. Free radical-induced injury can explain many clinical conditions.