Induction of reactive oxygen species by diphenyl diselenide is preceded by changes in cell morphology and permeability in Saccharomyces cerevisiae

Free Radic Res. 2017 Jul-Aug;51(7-8):657-668. doi: 10.1080/10715762.2017.1355054. Epub 2017 Aug 25.

Abstract

Organoselenium compounds, such as diphenyl diselenide (PhSe)2 and phenylselenium zinc chloride (PhSeZnCl), show protective activities related to their thiol peroxidase activity. However, depending on experimental conditions, organoselenium compounds can cause toxicity by oxidising thiol groups of proteins and induce the production of reactive oxygen species (ROS). Here, we analysed the toxicity of (PhSe)2 and PhSeZnCl in yeast Saccharomyces cerevisiae. Cell growth of S. cerevisiae after 1, 2, 3, 4, 6, and 16 h of treatment with 2, 4, 6, and 10 μM of (PhSe)2 was evaluated. For comparative purpose, PhSeZnCl was analysed only at 16 h of incubation at equivalent concentrations of selenium (i.e. 4, 8, 12, and 20 μM). ROS production (DCFH-DA), size, granularity, and cell membrane permeability (propidium iodide) were determined by flow cytometry. (PhSe)2 inhibited cell growth at 2 h (10 μM) of incubation, followed by increase in cell size. The increase of cell membrane permeability and granularity (10 μM) was observed after 3 h of incubation, however, ROS production occurs only at 16 h of incubation (10 μM) with (PhSe)2, indicating that ROS overproduction is a more likely consequence of (PhSe)2 toxicity and not its determinant. All tested parameters showed that only concentration of 20 μM induced toxicity in samples incubated with PhSeZnCl. In summary, the results suggest that (PhSe)2 toxicity in S. cerevisiae is time and concentration dependent, presenting more toxicity when compared with PhSeZnCl.

Keywords: Diphenyl diselenide; Saccharomyces cerevisiae; phenylselenium zinc chloride; reactive oxygen species; toxicity.

MeSH terms

  • Benzene Derivatives / pharmacology*
  • Cell Membrane Permeability / drug effects*
  • Chlorides / pharmacology
  • Organoselenium Compounds / pharmacology*
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism*
  • Saccharomyces cerevisiae / drug effects*
  • Selenium Compounds / pharmacology
  • Sulfhydryl Compounds / pharmacology
  • Zinc Compounds / pharmacology

Substances

  • Benzene Derivatives
  • Chlorides
  • Organoselenium Compounds
  • Reactive Oxygen Species
  • Selenium Compounds
  • Sulfhydryl Compounds
  • Zinc Compounds
  • phenylselenol
  • diphenyldiselenide
  • zinc chloride