A preliminary investigation into the impact of a pesticide combination on human neuronal and glial cell lines in vitro

PLoS One. 2012;7(8):e42768. doi: 10.1371/journal.pone.0042768. Epub 2012 Aug 3.

Abstract

Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and neuronal cells respectively. Over 48h, all three agents showed significant reductions in cellular ATP, at concentrations that were more than tenfold lower than those which significantly impaired cellular viability. The effects on energy metabolism were reflected in their marked toxic effects on mitochondrial membrane potential. In addition, evidence of oxidative stress was seen in terms of a fall in cellular thiols coupled with increases in the expression of enzymes associated with reactive species formation, such as GSH peroxidase and superoxide dismutase. The glial cell line showed significant responsiveness to the toxin challenge in terms of changes in antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater vulnerability to toxicity, which was reflected in significant increases in caspase-3 expression, which is indicative of the initiation of apoptosis. Cyprodinil was the most toxic agent individually, although oxidative stress-related enzyme gene expression increases appeared to demonstrate some degree of synergy in the presence of the combination of agents. This report suggests that the impact of some pesticides, both individually and in combinations, merits further study in terms of their impact on human cellular health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Benzimidazoles / metabolism
  • Carbocyanines / metabolism
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Dioxoles / toxicity
  • Energy Metabolism / drug effects
  • Gene Expression Regulation / drug effects
  • Glutathione / metabolism
  • Humans
  • Inactivation, Metabolic
  • Inhibitory Concentration 50
  • Neuroglia / drug effects*
  • Neuroglia / metabolism*
  • Neurons / drug effects*
  • Neurons / enzymology
  • Neurons / metabolism*
  • Pesticides / toxicity*
  • Polymerase Chain Reaction
  • Pyrimidines / toxicity
  • Pyrroles / toxicity

Substances

  • Benzimidazoles
  • Carbocyanines
  • Dioxoles
  • Pesticides
  • Pyrimidines
  • Pyrroles
  • 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine
  • cyprodinil
  • pyrimethanil
  • Adenosine Triphosphate
  • Caspase 3
  • fludioxonil
  • Glutathione

Grants and funding

This study received financial support from The Marchig Animal Welfare Trust Edinburgh, United Kingdom (www.marchigtrust.org), as well as the Union Belge pour l'Abolition de l'Expérimentation sur Animaux Vivants (UBAEAV, Rue H. van Zuylen 21, 1180 Bruxelles Tél: 02/376 82 83 Bruxelles, Belgium. In addition, Generations Futures, Paris, France (http://www.mdrgf.org)also contributed to the funding of the work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.