Document Detail


Oral bioavailability of glyphosate: studies using two intestinal cell lines.
MedLine Citation:
PMID:  15683179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glyphosate 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 [14C]-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 x 10(11) binding sites/cell were estimated from bound [14C]. Exposure of Caco-2 cells to > or =10 mg/ml glyphosate reduced transmembrane electrical resistance (TEER) by 82 to 96% and increased permeability to [3H]-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.
Authors:
Luba Vasiluk; Linda J Pinto; Margo M Moore
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Environmental toxicology and chemistry / SETAC     Volume:  24     ISSN:  0730-7268     ISO Abbreviation:  Environ. Toxicol. Chem.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-02-01     Completed Date:  2005-03-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8308958     Medline TA:  Environ Toxicol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-60     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
Biological Availability
Biological Transport
Cell Line
Cell Membrane
Cell Survival / drug effects
Cytoskeleton / drug effects
Dose-Response Relationship, Drug
Glycine / analogs & derivatives*,  pharmacokinetics,  toxicity*
Herbicides / pharmacokinetics,  toxicity*
Humans
Intestinal Absorption
Intestinal Mucosa / drug effects*,  metabolism
Mannitol / pharmacokinetics
Membrane Potentials / drug effects
Rats
Chemical
Reg. No./Substance:
0/Actins; 0/Herbicides; 1071-83-6/glyphosate; 56-40-6/Glycine; 69-65-8/Mannitol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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