Acute exposure to a glyphosate-containing herbicide formulation inhibits Complex II and increases hydrogen peroxide in the model organism Caenorhabditis elegans.
C. elegans; Glyphosate; Hydrogen peroxide; Mitochondrial inhibition; Oxygen consumption; Reactive oxygen species
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 \textless 0.05). When Complex II activity was further assessed, inhibition was observed in all TD-treated groups ((*)p \textless 0.05). Complex IV activity, however, was not adversely affected by TD. This electron transport chain inhibition also resulted in reduced ATP levels ((*)p \textless 0.05). Furthermore, hydrogen peroxide levels, but not other ROS, were increased ((*)p \textless 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.
Burchfield Shelbie L; Bailey Denise C; Todt Callie E; Denney Rachel D; Negga Rekek; Fitsanakis Vanessa A
Environmental toxicology and pharmacology
2019
2019-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.etap.2018.12.019" target="_blank" rel="noreferrer noopener">10.1016/j.etap.2018.12.019</a>
Acute exposure to a glyphosate-containing herbicide formulation inhibits Complex II and increases hydrogen peroxide in the model organism Caenorhabditis elegans.
C. elegans; Glyphosate; *hydrogen peroxide; Mitochondrial inhibition; Oxygen Consumption; *Reactive oxygen species; Animals; Reactive Oxygen Species/metabolism; Adenosine Triphosphate/metabolism; Herbicides/*toxicity; Caenorhabditis elegans/*drug effects/metabolism; Electron Transport Complex II/*antagonists & inhibitors/metabolism; Glycine/*analogs & derivatives/toxicity
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.
Burchfield Shelbie L; Bailey Denise C; Todt Callie E; Denney Rachel D; Negga Rekek; Fitsanakis Vanessa A
Environmental toxicology and pharmacology
2019
2019-02
<a href="http://doi.org/10.1016/j.etap.2018.12.019" target="_blank" rel="noreferrer noopener">10.1016/j.etap.2018.12.019</a>
Chronic exposure to a glyphosate-containing pesticide leads to mitochondrial dysfunction and increased reactive oxygen species production in Caenorhabditis elegans
C. elegans; Glyphosate; Hydrogen peroxide; Mitochondrial inhibition; oxidative stress; Toxicology; Environmental Sciences & Ecology; Pharmacology & Pharmacy; parkinsons-disease; brain; alzheimers-disease; mechanisms; degeneration; species; neurodegenerative diseases; 6-ohda; C. elegans; complex-i; Herbicide; Reactive oxygen
Glyphosate-containing herbicides are among the most widely-used in the world. Although glyphosate itself is relatively non-toxic, growing evidence suggests that commercial herbicide formulations may lead to increased oxidative stress and mitochondrial inhibition. In order to assess these mechanisms in vivo, we chronically (24 h) exposed Caenorhabditis elegans to various concentrations of the glyphosate-containing herbicide TouchDown (TD). Following TD exposure, we evaluated the function of specific mitochondrial electron transport chain complexes. Initial oxygen consumption studies demonstrated inhibition in mid- and high-TD concentration treatment groups compared to controls. Results from tetramethylrhodamine ethyl ester and ATP assays indicated reductions in the proton gradient and ATP levels, respectively. Additional studies were designed to determine whether TD exposure resulted in increased reactive oxygen species (ROS) production. Data from hydrogen peroxide, but not superoxide or hydroxyl radical, assays showed statistically significant increases in this specific ROS. Taken together, these data indicate that exposure of Caenorhabditis elegans to TD leads to mitochondrial inhibition and hydrogen peroxide production.
Bailey D C; Todt C E; Burchfield S L; Pressley A S; Denney R D; Snapp I B; Negga R; Traynor W L; Fitsanakis V A
Environmental Toxicology and Pharmacology
2018
2018-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.etap.2017.11.005" target="_blank" rel="noreferrer noopener">10.1016/j.etap.2017.11.005</a>