Mercury toxic effects on the intestinal mucosa assayed on a bicameral in vitro model: Possible role of inflammatory response and oxidative stress

Abstract

Exposure to mercury (Hg) mostly occurs through diet, where it is mainly found as inorganic Hg [Hg(II)] or methylmercury (MeHg). In vivo studies have linked its exposure with neurological and renal diseases, however, its toxic effects upon the gastrointestinal tract are largely unknown. In order to evaluate the effect of Hg on intestinal mucosa, a bicameral system was employed with co-cultures of Caco-2 and HT29-MTX intestinal epithelial cells and THP-1 macrophages. Cells were exposed to Hg(II) and MeHg (0.1, 0.5, 1 mg/L) during 11 days. The results evidenced a greater pro-inflammatory response in cells exposed to Hg with increments of IL-8 (15–126%) and IL-1β release (39–63%), mainly induced by macrophages which switched to a M1 phenotype. A pro-oxidant response was also observed in both cell types with an increase in ROS/RNS levels (44–140%) and stress proteins expression. Intestinal cells treated with Hg displayed structural abnormalities, hypersecretion of mucus and defective tight junctions. An increased paracellular permeability (123–170%) at the highest concentrations of Hg(II) and MeHg and decreased capacity to restore injuries in the cell monolayer were also observed. All these toxic effects were governed by various inflammatory signalling pathways (p38 MAPK, JNK and NF-κB).