Glyphosate-induced injury in neurons, endothelial cells and myoblasts is mediated by ROS production

Abstract

Background Glyphosate (N-(phosphonomethyl) glycine) is the active compound of a large part of non-selective herbicides, being the most used in agriculture worldwide since middle 70s. Glyphosate acts as an inhibitor of the shikimate pathway, which is present only in plants and some microorganisms. Despite this specific mechanism of action, the safety of glyphosate in mammals is still controversial. Aim This study aims to elucidate the direct biological effects of glyphosate and AMPA (one of its major metabolites), in three in vitro mammalian cell lines: neurons, myoblasts and endothelial cells. Samples are treated with different concentrations of glyphosate (5, 10 and 20 mM) or AMPA (10 and 20 mM), for 1, 2 or 24 hours. Cells are assessed for viability, ROS production and phenotypical changes. Results Glyphosate differentially affects neurons, endothelial cells and myoblasts, with a higher susceptibility of neurons and a higher tolerance of myoblasts. In all cell types, the response is dose-dependent. In terms of ROS production, results are in accordance to the pattern of viability. Morphology shows signs of cavitation of plasma membranes and intracellular compartments. Similarly, AMPA treatment reproduced the same effects in all cell types, but to a lower extent. Discussion Considering the future exposure to low but constant levels of glyphosate, it is of pivotal importance to elucidate its mechanism of actions in mammalian cells. In light of our results, we hypothesize an involvement of mitochondria in the effects of glyphosate. Different amount of mitochondria and antioxidant enzymes, in the different cell types, will be investigated as a prosecution of the study.