The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells.
Deoxynivalenol (DON) is a mycotoxin belonging to the tricothecene family that has many toxic effects in animals, including diarrhea and weight loss. Using the human epithelial intestinal cell line HT-29-D4 as an in vitro model, we studied the effect of DON on the uptake of different classes of nutrients, including sugars, amino acids and lipids. At low concentrations (below 10 micro mol/L), DON selectively modulated the activities of intestinal transporters: the D-glucose/D-galactose sodium-dependent transporter (SGLT1) was strongly inhibited by the mycotoxin (50% inhibition at 10 micro mol DON, P < 0.05), followed by the D-fructose transporter GLUT5 (42% inhibition at 10 micro mol/L, P < 0.001), active and passive L-serine transporters (30 and 38% inhibition, respectively, at 10 micro mol/L, P < 0.05). The passive transporters of D-glucose (GLUT) were slightly inhibited by DON (15% inhibition at 1 micro mol/L, P < 0.01), whereas the transport of palmitate was increased by 35% at 10 micro mol/L DON (P < 0.001). In contrast, the uptake of cholesterol was not affected by the mycotoxin. At high concentrations (100 micro mol/L), SGLT1 activity was inhibited by 76% (P < 0.01), whereas the activities of all other transporters were increased. The selective effects of DON on intestinal transporters were mimicked by cycloheximide and deoxycholate, suggesting that inhibition of protein synthesis and induction of apoptosis are the main mechanisms of DON toxicity in intestinal cells.
Maresca
Marc
M
Institut Méditerranéen de Recherche en Nutrition, Unité Mixte de Recherche-Institut National de la Recherche Agronomique, Faculté des Sciences de Saint-Jérôme, Marseille, France.
Mahfoud
Radhia
R
Garmy
Nicolas
N
Fantini
Jacques
J
D000596:Amino Acids / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D050260:Carbohydrate Metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003513:Cycloheximide / Q000633:toxicity; D003840:Deoxycholic Acid / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D014255:Trichothecenes / Q000633:toxicity*
D000596:Amino Acids; D011500:Protein Synthesis Inhibitors; D014255:Trichothecenes; D003840:Deoxycholic Acid; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase; C007262:deoxynivalenol