Glyphosate commercial formulation causes cytotoxicity, oxidative effects, and apoptosis on human cells: differences with its active ingredient

Int J Toxicol. 2014 Jan-Feb;33(1):29-38. doi: 10.1177/1091581813517906. Epub 2014 Jan 16.

Abstract

In the present study, the effects on oxidative balance and cellular end points of glyphosate, aminomethylphosphonic acid (AMPA), and a glyphosate formulation (G formulation) were examined in HepG2 cell line, at dilution levels far below agricultural recommendations. Our results show that G formulation had toxic effects while no effects were found with acid glyphosate and AMPA treatments. Glyphosate formulation exposure produced an increase in reactive oxygen species, nitrotyrosine formation, superoxide dismutase activity, and glutathione (GSH) levels, while no effects were observed for catalase and GSH-S-transferase activities. Also, G formulation triggered caspase 3/7 activation and hence induced apoptosis pathway in this cell line. Aminomethylphosphonic acid exposure produced an increase in GSH levels while no differences were observed in other antioxidant parameters. No effects were observed when the cells were exposed to acid glyphosate. These results confirm that G formulations have adjuvants working together with the active ingredient and causing toxic effects that are not seen with acid glyphosate.

Keywords: apoptosis; cytotoxicity; glyphosate; in vtro; oxidative stress.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Pharmaceutic / toxicity*
  • Apoptosis / drug effects*
  • Chemistry, Pharmaceutical
  • Drug Synergism
  • Glutathione / agonists
  • Glutathione / metabolism
  • Glycine / analogs & derivatives*
  • Glycine / toxicity
  • Glyphosate
  • Hep G2 Cells
  • Hepatocytes / cytology
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Herbicides / chemistry
  • Herbicides / toxicity*
  • Humans
  • Isoxazoles
  • Lethal Dose 50
  • Organophosphonates / toxicity
  • Osmolar Concentration
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / metabolism
  • Tetrazoles
  • Tyrosine / agonists
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Up-Regulation / drug effects*

Substances

  • Adjuvants, Pharmaceutic
  • Herbicides
  • Isoxazoles
  • Organophosphonates
  • Reactive Oxygen Species
  • Tetrazoles
  • 3-nitrotyrosine
  • Tyrosine
  • Superoxide Dismutase
  • Glutathione
  • 2-amino-3-(3-hydrox-5(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl)propionic acid
  • Glycine