Intracellular pro-oxidant activity of melatonin deprives U937 cells of reduced glutathione without affecting glutathione peroxidase activity

Intracellular Pro-oxidant Activity of Melatonin Deprives U937 Cells of Reduced Glutathione without Affecting Glutathione Peroxidase Activity The neurotoxicity of a number of compounds like kainic acid, haloperidol, and the cellular toxicity of hydrogen peroxide is inhibited by melatonin administration. In some cases, the accompanying decrease in reduced glutathione (GSH) levels are also prevented by melatonin administration. On basis of these findings, melatonin was considered to exert its physiological and pharmacological effects, at least partly, via its antioxidant activity. However, authors observed only a limited antioxidant activity of melatonin in several systems. It was long believed that melatonin might counteract intracellular oxidative stress because it was shown to potentiate antioxidant endogenous defences, and to increase the activity of many antioxidant enzymes. However, it is now becoming evident that when radicals are measured within cells, melatonin increases, rather than decreasing, radical production. Herein we demonstrate a pro-oxidant effect of melatonin in U937 cells by showing an increase of intracellular oxidative species and a depletion of glutathione (GSH). The activity of glutathione peroxidase is not modified by melatonin treatment as it does occur in other experimental models. Experiments are in progress to investigate how melatonin may act on U937 cell metabolism and may directly or indirectly stimulate oxidative radical production.