Acute exposure to a glyphosate-containing herbicide formulation inhibits Complex II and increases hydrogen peroxide in the model organism Caenorhabditis elegans

Environ Toxicol Pharmacol. 2019 Feb;66:36-42. doi: 10.1016/j.etap.2018.12.019. Epub 2018 Dec 24.

Abstract

Glyphosate-based herbicides, such as Touchdown (TD) and Roundup, are among the most heavily-used herbicides in the world. While the active ingredient is generally considered non-toxic, the toxicity resulting from exposure to commercially-sold formulations is less clear. In many cases, cell cultures or various model organisms exposed to glyphosate formulations show toxicity and, in some cases, lethality. Using Caenorhabditis elegans, we assessed potential toxic mechanisms through which a highly-concentrated commercial formulation of TD promotes neurodegeneration. Following a 30-min treatment, we assayed mitochondrial electron transport chain function and reactive oxygen species (ROS) production. Initial oxygen consumption studies indicated general mitochondrial inhibition compared to controls (*p < 0.05). When Complex II activity was further assessed, inhibition was observed in all TD-treated groups (*p < 0.05). Complex IV activity, however, was not adversely affected by TD. This electron transport chain inhibition also resulted in reduced ATP levels (*p < 0.05). Furthermore, hydrogen peroxide levels, but not other ROS, were increased (*p < 0.05). Taken together, these data indicate that commercially-available formulations of TD may exert neurotoxicity through Complex II (succinate dehydrogenase) inhibition, decreased ATP levels, and increased hydrogen peroxide production.

Keywords: C. elegans; Glyphosate; Hydrogen peroxide; Mitochondrial inhibition; Oxygen consumption; Reactive oxygen species.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / metabolism
  • Electron Transport Complex II / antagonists & inhibitors*
  • Electron Transport Complex II / metabolism
  • Glycine / analogs & derivatives*
  • Glycine / toxicity
  • Herbicides / toxicity*
  • Reactive Oxygen Species / metabolism

Substances

  • Herbicides
  • Reactive Oxygen Species
  • glyphosate
  • Adenosine Triphosphate
  • Electron Transport Complex II
  • Glycine