Metabolism and transfer of the mycotoxin zearalenone in human intestinal Caco-2 cells.
The mycotoxin zearalenone (ZEA) is found worldwide as contaminant in cereals and grains. It is implicated in reproductive disorders and hyperestrogenic syndromes in animals and humans exposed by food. We investigated metabolism and transfer of ZEA using the human Caco-2 cell line as a model of intestinal epithelial barrier. Cells exposed to 10-200 microM ZEA showed efficacious metabolism of the toxin. alpha-zearalenol and beta-zearalenol were the measured preponderant metabolites (respectively 40.7+/-3.1% and 31.9+/-4.9% of total metabolites, after a 3h exposure to 10 microM ZEA), whereas ZEA-glucuronide and alpha-zearalenol glucuronide were less produced (respectively 8.2+/-0.9% and 19.1+/-1.3% of total metabolites, after a 3h exposure to 10 microM ZEA). Cell production of reduced metabolites was strongly inhibited by alpha-and beta-hydroxysteroid dehydrogenase inhibitors, and Caco-2 cells exhibited alpha-hydroxysteroid dehydrogenase type II and beta-hydroxysteroid dehydrogenase type I mRNA. After cell apical exposure to ZEA, alpha-zearalenol was preponderantly found at the basal side, whereas beta-zearalenol and both glucuronides were preferentially excreted at the apical side. As alpha-zearalenol shows the strongest estrogenic activity, the preferential production and basal transfer of this metabolite suggests that intestinal cells may contribute to the manifestation of zearalenone adverse effects.
Videmann
Bernadette
B
UMR 1233 INRA-ENVL-ISARA, Métabolisme et Toxicologie Comparée des Xénobiotiques, Ecole Nationale Vétérinaire de Lyon, 1, avenue Bourgelat, BP 83, 69280 Marcy l'Etoile, France.
Mazallon
Michelle
M
Tep
Jonathan
J
Lecoeur
Sylvaine
S
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D001692:Biological Transport; D018938:Caco-2 Cells; D004968:Estrogens, Non-Steroidal / Q000378:metabolism*; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism; D009183:Mycotoxins / Q000378:metabolism*; D015025:Zearalenone / Q000378:metabolism*
D004968:Estrogens, Non-Steroidal; D009183:Mycotoxins; D015025:Zearalenone; D015096:3-Hydroxysteroid Dehydrogenases