Effect of subchronic exposure to inorganic arsenic on the structure and function of the intestinal epithelium

Inorganic arsenic (As), the most toxic form of As found in water and food, is considered a human carcinogen. Numerous studies show its systemic toxicity, describing pathologies associated with chronic exposure. The main pathway of exposure to inorganic As is oral, but many of the events that occur during its passage through the gastrointestinal tract are unknown. This study evaluates the effect of subchronic exposure to inorganic As [As(III): 0.025–0.1 mg/L; As(V): 0.25–1 mg/L, up to 21 days] on the intestinal epithelium, using Caco-2 cells as in vitro model. Inorganic As produces a pro-inflammatory response throughout the exposure time, with an increase in IL-8 release (up to 488%). It also causes changes in the program of cell proliferation and differentiation, which leads to impairment of the cell repair process. In addition, subchronic exposure affects the epithelial structure, causing loss of microvilli, fundamental structures in the processes of intestinal absorption and digestion. Moreover, the exposure affects the epithelial barrier function, evidenced by an increase of Lucifer Yellow transport (103–199%). Therefore, it can be concluded that subchronic exposure to inorganic As can alter intestinal homeostasis, affecting the mucosal layer, which performs the most important functions of the intestinal wall.This work was supported by the Spanish Ministry of Economy and Competitiveness (AGL2015-68920-R), for which the authors are deeply indebted. Gabriela de Matuoka e Chiocchetti received a fellowship from the Brazilian Government (CAPES-proceso BEX1086/14-6).Peer reviewe