Prooxidant effects of melatonin: a brief review

Melatonin acts classically through the widely expressed G protein-coupled membrane receptors MT1 and MT2, respectively. The functional role of the MT receptors is not fully clear with multiple effects, such as effects on the circadian, reproductive, immune, cardiovascular, and intestinal systems, being suggested. In addition to receptor-mediated effects, melatonin also acts as a potent antioxidant and it is quite evident that melatonin and its metabolites efficiently reduce oxidative damage to proteins, lipids, and DNA and also exert protective effects on mitochondria. The potent antioxidant activity of melatonin stems from various complex mechanisms, including direct scavenging of radicals, stimulation of antioxidant enzymes, and maintenance of mitochondrial homeostasis. However, about a dozen experimental studies also suggest that melatonin can exert prooxidant effects under certain circumstances. Involvement of calmodulin and the mitochondrial respiratory chain may be potential targets for the prooxidant effects of melatonin. This review briefly summarizes the physiobiochemistry of melatonin, including its antioxidative functions, and summarizes and discusses studies showing prooxidant effects of this hormone.