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Oral bioavailability of glyphosate: Studies using two intestinal cell lines
Author(s) -
Vasiluk Luba,
Pinto Linda J.,
Moore Margo M.
Publication year - 2005
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1897/04-088r.1
Subject(s) - bioavailability , glyphosate , environmental chemistry , biology , chemistry , microbiology and biotechnology , pharmacology
Gyphosate is a commonly used nonselective herbicide that inhibits plant growth through interference with the production of essential aromatic amino acids. In vivo studies in mammals with radiolabeled glyphosate have shown that 34% of radioactivity was associated with intestinal tissue 2 h after oral administration. The aim of our research was to investigate the transport, binding, and toxicity of glyphosate to the cultured human intestinal epithelial cell line, Caco‐2, and the rat small intestinal crypt‐derived cell line, ileum epithelial cells‐18 (IEC‐18). An in vitro analysis of the transport kinetics of [ 14 C]‐glyphosate showed that 4 h after exposure, approximately 8% of radiolabeled glyphosate moved through the Caco‐2 monolayer in a dose‐dependent manner. Binding of glyphosate to cells was saturable and approximately 4 × 10 11 binding sites/cell were estimated from bound [ 14 C]. Exposure of Caco‐2 cells to ≥10 mg/ml glyphosate reduced transmembrane electrical resistance (TEER) by 82 to 96% and increased permeability to [ 3 H]‐mannitol, indicating that paracellular permeability increased in glyphosate‐treated cells. At 10‐mg/ml glyphosate, both IEC‐18 and Caco‐2 cells showed disruption in the actin cytoskeleton. In Caco‐2 cells, significant lactate dehydrogenase leakage was observed when cells were exposed to 15 mg/ml of glyphosate. These data indicate that at doses >10 mg/ml, glyphosate significantly disrupts the barrier properties of cultured intestinal cells.