Search

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 (H2O2). 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 H2O2-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. [ABSTRACT FROM AUTHOR]

The β-carboline alkaloids found in medical plants and in a variety of foods, beverages and cigarette smoke have a range of action in various biological systems. In vitro studies have demonstrated that these alkaloids can act as scavengers of reactive oxygen species. In this paper, we report the in vivo antioxidative properties of the aromatic (harmane, harmine, harmol) and dihydro-β-carbolines (harmaline and harmalol) studied by using Saccharomyces cerevisiae strains proficient and deficient in antioxidant defenses. Their antimutagenic activity was also assayed in S. cerevisiae and the antigenotoxicity was tested by the comet assay in V79 cell line, when both eukaryotic systems were exposed to H2O2. We show that the alkaloids have a significant protective effect against H2O2 and paraquat oxidative agents in yeast cells, and that their ability to scavenge hydroxyl radicals contributes to their antimutagenic and antigenotoxic effects. [ABSTRACT FROM AUTHOR]