Lung Inflammation from Single and Repetitive Exposure to Glyphosate

Abstract

Background: Glyphosate is an active ingredient in herbicides used in agriculture worldwide. Exposure to glyphosate has been associated with respiratory dysfunctions in agricultural workers. However, the ability of glyphosate to induce inflammation in the lung is not well studied. Therefore, we evaluated lung inflammatory response to glyphosate at agricultural relevant dose for single and repetitive exposures. Methods: Male C57BL/6 mice were intranasally exposed to glyphosate (1 μg/40 μl) for 1-day or once daily for 5-days, and 10-days. After the exposure periods, mice were euthanized to collect the bronchoalveolar lavage (BAL) fluid and lung tissue. Results: Repetitive exposure to glyphosate for 5-days and 10-days showed an increase of neutrophils in BAL fluid and eosinophil peroxidase levels in lungs, a marker for eosinophils. Leukocyte infiltration in lungs was further confirmed through lung histology. Th2 cytokines including IL-5 and IL-13 were increased in BAL fluid after 10-days of glyphosate exposure whereas IL-4 was not increased. Lung sections from all glyphosate groups showed higher expression for ICAM-1, VCAM-1, and vWF adhesion molecules. TLR-4 and TLR-2 expression was increased in lungs after repetitive exposure to glyphosate. Conclusions: We conclude that repetitive exposure to glyphosate induces migration of neutrophils and eosinophils and release of Th2 cytokines. This study, for the first time, provides evidence for the role of ICAM-1, VCAM-1 and vWF in lungs of glyphosate-treated animals.