Melatonin, active oxygen species and neurological damage

Recently described actions of melatonin and other antioxidants are currently of great interest in the clinical arena. The overall phenomenon by which oxygen destroys molecular integrity is referred to as oxidative stress, and the damage inflicted has been linked to a variety of diseases and to aging. In addition to its direct free radical-detoxifying activity, melatonin also functions as an indirect antioxidant by changing the activity of enzymes that metabolize active oxygen species to inactive products. Besides inhibiting the prooxidative enzyme NOS, melatonin-at least when given at pharmacological levels-stimulates the activity of several antioxidative enzymes. Melatonin was also recently shown to prevent membrane fluidity changes associated with lipid peroxidation. Melatonin has been shown to protect against a large number of models of neurodegeneration in animals that involve free radical damage; however, clinical studies using this molecule have yet to be performed. Considering the apparent virtual absence of either acute or chronic toxicity of melatonin, its use in humans to avert free radical damage should be considered.