The mycotoxin ochratoxin A alters intestinal barrier and absorption functions but has no effect on chloride secretion

Ochratoxin A (OTA) is a mycotoxin that contaminates cereals and animal feed and causes nephropathy to a variety of animal species. OTA is also known a s a potent immunotoxic, teratogenic, and carcinogenic mycotoxin. In additio n, OTA ingestion induces intestinal injuries, including inflammation and di arrhea. With the aim to study the cellular mechanisms associated with the i ntestinal toxicity of OTA, two human epithelial intestinal cell lines (HT-2 9-D4 and Caco-2-14 cells), widely used as in vitro models for the intestina l epithelium, were incubated with OTA. The main effects of the mycotoxin we re an inhibition of cellular growth and a dramatic decrease of transepithel ial resistance in both cell lines. Since transepithelial resistance reflect s the organization of tight junctions over the cell monolayer, these data m ay suggest that OTA could potentiate its own absorption through paracellula r pathways. OTA induced a 60% decrease of sodium-dependent glucose absorpti on but increased the absorption of fructose and L-serine in HT-29-D4 cells. Moreover, the mycotoxin did not inhibit the cAMP-dependent chloride secret ion through the cystic fibrosis transmembrane conductance regulator channel . The inhibitory effect of OTA on active glucose transport was partially an tagonized by L-phenylalanine, but not by a-tocopherol, suggesting that the toxicity of OTA could result from an inhibition of protein synthesis, rathe r than an induction of lipid peroxidation. In particular, OTA affected the protein content of plasma membrane microdomains, which are known to regulat e tight junction assembly and intestinal transport activity. Taken together , these data showed that OTA alters both barrier and absorption functions o f the intestinal epithelium. (C) 2001 Academic Press.