Antioxidant and anti-mutagenic effects of ebselen in yeast and in cultured mammalian V79 cells

Abstract

Ebselen has a wide spectrum of interesting therapeutic actions including antioxidant, cytoprotective, neuroprotective and anti-inflammatory activities. Since its antioxidant effect is very well known, this paper links the effects of ebselen in redox cellular status to its possible involvement in the maintenance of the integrity of genomic information by using Saccharomyces cerevisiae strains proficient and deficient in antioxidant defences and the mammalian V79 cell line. Using the alkaline comet assay, we showed that 5-10 μM ebselen does not induce DNA damage in V79 cells. Similarly, these same concentrations diminished the extent of the DNA damage induced by hydrogen peroxide (H 2O2). The modified comet assay using DNA glycosylases (formamidopyrimidine-DNA glycosylase and endonuclease II) showed that after pre-treatment with ebselen followed by exposure to H2O2, oxidative damage as recognized by these enzymes was significantly lower. In the same way, ebselen showed strong activity against H2O 2-induced oxidative damage in the anti-mutagenic assay using S.cerevisiae N123 strain and in the antioxidative assay by using S.cerevisiae strains lacking antioxidant defences. This antioxidant effect was more pronounced for the gpx3 Δ mutant, which indicated that ebselen acts by mimicking the GPx3 catalytic activity. The results confirm that ebselen is involved in antioxidant defence and that its antioxidant ability contributes to its anti-mutagenic and anti-genotoxic action. © The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.