Limited Effectiveness of Antioxidants in the Protection of Yeast Defective in Antioxidant Proteins

Abstract

Efficacy of several antioxidants in the protection of the yeast Saccharomyces cerevisiae mutants deficient in CuZnSOD and deficient in glutaredoxin 5 to growth restriction induced by oxidants was studied. Ascorbate and glutathione protected the Deltasod1 and Deltagrx5 mutants against the effects of t-butyl hydroperoxide and cumene hydroperoxide, Deltasod1 mutants against oxytetracycline and Deltagrx5 mutants against menadione and 2,2'-azobis-(2-amidinopropane). However, Tempol, Trolox and melatonin were much less effective, showing prooxidative effects and, at high concentrations, hampering the growth of the mutants in the absence of exogenous oxidants. These results point to a complication of cellular effects of antioxidants by their prooxidative effects and to the usefulness of cellular tests to evaluate the biological effectiveness of antioxidants.

Ascorbate and thiol antioxidants abolish sensitivity of yeast Saccharomyces cerevisiae to disulfiram

“…4a, b). The same pattern of antioxidant action was found when studying rescue of Δ sod1 mutant cells from other oxidants including tert -butyl hydroperoxide, cumene hydroperoxide, menadione, juglone, hypochlorite, chlorite, oxytetracycline, acrolein, acrylamide, and hypertonic stress (Koziol et al 2005; Lewinska et al 2004; Kwolek-Mirek et al 2009; Kwolek-Mirek et al 2011), which suggests that DSF induces oxidative stress by a mechanism similar to that of other oxidants.…”

A role for yeast glutaredoxin genes in selenite-mediated oxidative stress

“…A cytoprotective effect of glutathione against organic peroxides and menadione, a superoxide generating agent, on cells lacking the GRX5 gene (Lewinska et al, 2004) and against heavy metals toxicity to the mutant devoid of antioxidative Ure2 protein (Lewinska and Bartosz, 2007) was reported by us previously. However, adverse The Dgrx1Dgrx2 and Dgrx5 mutants with appropriate wild type controls (at a concentration of 10 8 cells/ml) were subjected to 2 mM selenite in 0.1 M phosphate buffer, pH 7.0, at 28 o C for 0 (control), 1, 2 and 3 h and then thiol content in 5% w/v TCA extracts of the cells was estimated with the Ellman reagent.…”

Suppressive Effects of Natural Compounds on Methionine Auxotrophy of a Cu,Zn-Superoxide Dismutase-Deficient Mutant of <i>Saccharomyces cerevisiae</i>

“…These antioxidants have been demonstrated to have effective antioxidant activities in various in vitro assays, and most compounds are ingredients in commercially available dietary supplements (Bouayed and Bohn, 2010;Bergström et al, 2012;Sadowska-antioxidants (AsA and thiol antioxidants) can suppress Met auxotrophy of the sod1∆ strain by exogenous supplementation. The same pattern of antioxidant action was found when studying the restoration of sod1∆ from oxidative stress-sensitive phenotypes (Lewinska et al, 2004;Kozioł et al, 2005;Tamura et al, 2010;Kwolek-Mirek et al, 2012) and a mutator phenotype (Nagira et al, 2013).…”