Antioxidant and anti-mutagenic effects of ebselen in yeast and in cultured mammalian V79 cells.
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 microM 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(2)O(2)). The modified comet assay using DNA glycosylases (formamidopyrimidine-DNA glycosylase and endonuclease II) showed that after pre-treatment with ebselen followed by exposure to H(2)O(2), oxidative damage as recognized by these enzymes was significantly lower. In the same way, ebselen showed strong activity against H(2)O(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 delta 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.
Miorelli
Simone Teresinha
ST
Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
Rosa
Renato Moreira
RM
Moura
Dinara Jaqueline
DJ
Rocha
Jaqueline Cesar
JC
Lobo
Larissa Aline Carneiro
LA
Henriques
João Antonio  Pêgas
JA
Saffi
Jenifer
J
D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D017353:Gene Deletion; D005979:Glutathione Peroxidase / Q000235:genetics; D006861:Hydrogen Peroxide / Q000633:toxicity; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
D016587:Antimutagenic Agents; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D029701:Saccharomyces cerevisiae Proteins; C042986:ebselen; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; C494438:HYR1 protein, S cerevisiae