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 as a potent immunotoxic, teratogenic, and carcinogenic mycotoxin. In addition, OTA ingestion induces intestinal injuries, including inflammation and diarrhea. With the aim to study the cellular mechanisms associated with the intestinal toxicity of OTA, two human epithelial intestinal cell lines (HT-29-D4 and Caco-2-14 cells), widely used as in vitro models for the intestinal epithelium, were incubated with OTA. The main effects of the mycotoxin were an inhibition of cellular growth and a dramatic decrease of transepithelial resistance in both cell lines. Since transepithelial resistance reflects the organization of tight junctions over the cell monolayer, these data may suggest that OTA could potentiate its own absorption through paracellular pathways. OTA induced a 60% decrease of sodium-dependent glucose absorption but increased the absorption of fructose and L-serine in HT-29-D4 cells. Moreover, the mycotoxin did not inhibit the cAMP-dependent chloride secretion through the cystic fibrosis transmembrane conductance regulator channel. The inhibitory effect of OTA on active glucose transport was partially antagonized by L-phenylalanine, but not by alpha-tocopherol, suggesting that the toxicity of OTA could result from an inhibition of protein synthesis, rather than an induction of lipid peroxidation. In particular, OTA affected the protein content of plasma membrane microdomains, which are known to regulate tight junction assembly and intestinal transport activity. Taken together, these data showed that OTA alters both barrier and absorption functions of the intestinal epithelium.
Maresca
M
M
Faculté des Sciences St-Jérôme, Institut Méditerranéen de Recherche en Nutrition, 13397 Marseille Cedex 20, France.
Mahfoud
R
R
Pfohl-Leszkowicz
A
A
Fantini
J
J
D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002712:Chlorides / Q000378:metabolism*; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007422:Intestines / Q000187:drug effects* / Q000502:physiology*; D007700:Kinetics; D009183:Mycotoxins / Q000494:pharmacology / Q000633:toxicity; D009793:Ochratoxins / Q000494:pharmacology* / Q000633:toxicity; D019108:Tight Junctions / Q000737:chemistry
D002712:Chlorides; D006017:Glycolipids; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A