Absorption of fumonisin B1 and aminopentol on an in vitro model of intestinal epithelium; the role of P-glycoprotein.
The aim of the present paper is to evaluate the absorption of fumonisin B1 and its principal metabolite, aminopentol on a human intestinal model, Caco-2 cells, cultured on semi-permeable inserts, that reproduces the two different intestinal compartments: luminal (apical) and serosal (basolateral) side. Following separate exposure in apical and in basolateral compartments, aminopentol passage through the cell layer (in particular from basolateral to apical direction) was shown, while it was not observed for the parent compound. The different aminopentol distribution between the two compartments of the culture system, and its variation in presence of verapamil or probenecid (P-gp and MRP inhibitors respectively), strongly suggests the involvement of P-glycoprotein in the influx/efflux mechanisms of aminopentol in the intestinal cells, reducing its oral bioavailability.
De Angelis
I
I
Department of Environment and Primary Prevention, Toxicity Mechanism Unit, Istituto Superiore di Sanità, viale Regina Elena 299, 00161 Rome, Italy. ideangel@iss.it
Friggè
G
G
Raimondi
F
F
Stammati
A
A
Zucco
F
F
Caloni
F
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018938:Caco-2 Cells; D002264:Carboxylic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology; D037341:Fumonisins / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009183:Mycotoxins / Q000493:pharmacokinetics* / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002264:Carboxylic Acids; D037341:Fumonisins; D009183:Mycotoxins; C110744:aminopentol; C056933:fumonisin B1; D014700:Verapamil; D011339:Probenecid