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Melatonin Attenuates Hydrogen Peroxide Toxicity in MCF7 Cells Only at Pharmacological Concentrations

1998; Elsevier BV; Volume: 250; Issue: 3 Linguagem: Inglês

10.1006/bbrc.1998.9370

1090-2104

William S. Baldwin, J. Carl Barrett,

Stress Responses and Cortisol

Melatonin is proposed to be oncostatic in mammary tissue, and one mechanism by which this hormone may elicit its possible oncostatic effect is as an oxygen radical scavenger. Therefore, we examined melatonin's abilities to act as an oxygen radical scavenger at physiological or pharmacological concentrations. Hydrogen peroxide at 400 μM killed 97% of treated MCF7 cells within 8 h, and following melatonin at 10−5and 10−4M concentrations only 76 and 64% of cells, respectively, were killed by hydrogen peroxide. However, melatonin at lower concentrations (10−7M) did not protect MCF7 cells. Moreover, pretreatment with melatonin (10−5or 10−7M) prior to hydrogen peroxide stress offered no further efficacy, and pretreatment with melatonin followed by the withdrawal of melatonin eliminated its protective effect from hydrogen peroxide toxicity. These findings indicate that melatonin acts directly as an antioxidant and does not stimulate antioxidant defenses in MCF7 cells that protect against hydrogen peroxide. Glutathione levels were examined to substantiate this hypothesis and were not altered by melatonin treatment. In conclusion, melatonin is an excellent oxygen radical scavenger at pharmacological concentrations, but not at physiological concentrations. Thus, loss of melatonin is unlikely to be important in oxidative scavenger mechanisms in human mammary cells.