Individual and Combined Effects of Commercial Glyphosate and Dicamba-Based Herbicide Formulations on Cytotoxicity, Oxidative Stress and Cell Death on Human Intestinal Caco-2 Cells.

Abstract

Pesticide contamination of food and environmental matrices represents a potential risk to human health. This study investigated the toxicological effects of commercial glyphosate and dicamba-based herbicide formulations, individually and in combination, on human intestinal epithelial Caco-2 cells. Cells were exposed to a concentration range of 0.1-10,000 mg/L for 24, 48, and 72 h to determine IC₅₀ values. Subsequent assays were conducted using concentrations based on the lowest IC₅₀ obtained and in the limits established by the Environmental Protection Agency for drinking water. After 48 h of exposure, glyphosate at the highest tested concentration, as well as co-exposure to glyphosate and dicamba, induced significant cytotoxicity, modulation of oxidative stress parameters, and alterations in antioxidant defenses, accompanied by increased rates of apoptosis and necrosis. Dicamba exposure alone also resulted in elevated apoptotic and necrotic cell populations. A reduction in N-acetyl-β-D-glucosaminidase activity was observed across most tested concentrations, suggesting impaired inflammatory response capacity. This work identified alterations in Caco-2 that impair cellular homeostasis by cytotoxicity, alterations in oxidative stress, antioxidant response, inflammation, apoptosis and necrosis. Future studies investigating inflammatory pathways, genetic damage, and assays with in vivo and in silico models are important to elucidate the mechanism of the cellular damage caused by exposure to these herbicides.