Mixtures of glyphosate and surfactant TN20 accelerate cell death via mitochondrial damage-induced apoptosis and necrosis.

Abstract

Glyphosate, a common herbicide, is not toxic under normal exposure circumstances. However, this chemical, when combined with a surfactant, is cytotoxic. In this study, the mechanism of the additive effect of glyphosate and TN-20, a common surfactant in glyphosate herbicides, was investigated. After exposure of rat H9c2 cells to glyphosate and TN-20 mixtures, following assays were performed: flow cytometry to determine the proportion of cells that underwent apoptosis and necrosis; western blotting to determine expression of mitochondrial proteins (Bcl-2 and Bax); immunological methods to evaluate translocation of cytochrome C; luminometric measurements to determine activity of caspases 3/7 and 9; and tetramethyl rhodamine methyl ester assay to measure mitochondrial membrane potentials. Bcl-1 intensity decreased while Bax intensity increased with exposure to increasing TN-20 and/or glyphosate concentrations. Caspase activity increased and mitochondrial membrane potential decreased only when the cells were exposed to a mixture of both TN-20 and glyphosate, but not after exposure to either one of these compounds. The results support the possibility that mixtures of glyphosate and TN-20 aggravate mitochondrial damage and induce apoptosis and necrosis. Throughout this process, TN-20 seems to disrupt the integrity of the cellular barrier to glyphosate uptake, promoting glyphosate-mediated toxicity.

• Authors: Young-hee Kim, Jung-rak Hong, Hyo-wook Gil, Ho-yeon Song, Sae-yong Hong
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 27 Issue 1 Pg. 191-7 (Feb 2013) ISSN: 1879-3177 [Electronic] England
• PMID: 23099315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Bax protein, rat
• Fats
• Proto-Oncogene Proteins c-bcl-2
• Surface-Active Agents
• bcl-2-Associated X Protein
• Polyethylene Glycols
• glyphosate
• Cytochromes c
• Caspases
• Glycine

Topics

• Animals
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Line
• Cytochromes c (metabolism)
• Fats (administration & dosage, toxicity)
• Glycine (administration & dosage, analogs & derivatives, toxicity)
• Mitochondria (drug effects)
• Necrosis (chemically induced, metabolism)
• Polyethylene Glycols (administration & dosage, toxicity)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Surface-Active Agents (administration & dosage, toxicity)
• bcl-2-Associated X Protein (metabolism)