Cadmium exacerbates dextran sulfate sodium-induced chronic colitis and impairs intestinal barrier

The potential health risk of environmental pollutant, cadmium, has become a public concern due to its widespread existence and long biological half-life. High-dose cadmium can induce various adverse outcomes, however, the chronic biological influences of cadmium at an environmental dosage and its mechanism remain largely unclear. Here, we investigated the effect of long-term exposure of cadmium at the environmental-relevant concentration on intestinal function. A chronic colitis mouse model was established through multiple cycles of dextran sulfate sodium (DSS) challenge and recovery. 200 nM cadmium in drinking water intensified colonic inflammation induced by DSS (histological score, DSS vs. DSS + Cd: 7.4 +/- 1.21 vs. 10.67 +/- 0.67, P< 0.05), including fecal occult bleeding and fecal consistency loss. Multiple inflammatory cytokines were significantly up-regulated by cadmium both in colon and plasma (P< 0.05). In addition, intestinal integrity was compromised by cadmium. Goblet cells were markedly reduced (ctrl vs. Cd: 48.33 +/- 3.07 vs. 37.5 +/- 2.14, P< 0.05) and plasma D-lactate (ctrl vs. Cd: 1.88 +/- 0.20 vs. 2.80 +/- 0.15, P < 0.01) and diamine oxidase (ctrl vs. Cd: 5.00 +/- 0.87 vs. 1121 +/- 2.17, P< 0.05) were increased in cadmium-treated mice, indicating an elevated intestinal permeability. In vitro results showed that long-term exposure of cadmium down-regulated the expression and membrane localization of adherent and tight junction proteins in a time-dependent manner. In conclusion, long-term exposure of environmental dose of cadmium aggravated DSS-induced chronic colitis and disrupted intestinal barrier and impaired the adherent and tight junction proteins. These findings provide a better understanding about the health risk of cadmium in the environment. (C) 2020 Elsevier B.V. All rights reserved.