title: 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.affiliation: Department of Immunology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Young-hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Jung-rak
authors.initials: JR
authors.lastname: Hong
authors.forename: Hyo-wook
authors.initials: HW
authors.lastname: Gil
authors.forename: Ho-yeon
authors.initials: HY
authors.lastname: Song
authors.forename: Sae-yong
authors.initials: SY
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D005223:Fats / Q000008:administration & dosage / Q000633:toxicity*; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000097797:Glyphosate
chemical_list: D020169:Caspases; D045304:Cytochromes c; D005223:Fats; D005998:Glycine; D011092:Polyethylene Glycols; D019253:Proto-Oncogene Proteins c-bcl-2; D013501:Surface-Active Agents; D051028:bcl-2-Associated X Protein; D000097797:Glyphosate; C494828:Bax protein, rat