Dietary nucleotide supplements in infant formula modify the expression of P-glycoprotein in the intestinal epithelium in vitro.
The effect of dietary nucleotides at concentrations found in supplemented infant formula on P-glycoprotein (P-gp) expression in colon cells was examined. We report that P-gp expression in colon cells was significantly decreased in a time- and concentration-dependent manner. When colon cells were co-cultured with lymphocytes, so as to mimic the involvement of gut-associated lymphoid tissue in normal gut pathophysiology, we observed a reversal of this effect with a demonstrated increase in P-gp expression. These findings have important implications on effects of nucleotide exposure on increasing drug bioavailability, reducing the capacity for xenobiotic efflux, and increasing the risk of inflammatory bowel disease in susceptible infants. Future studies are directed at defining both the mechanisms underlying these findings and effects of dietary nucleotide supplementation in vivo.
Bebawy
Mary
M
Faculty of Pharmacy, Sydney University, Australia. maryb@pharm.usyd.edu.au
Rasmussen
Christine
C
Sambasivam
Shwetha
S
Bao
Shisan
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019587:Dietary Supplements; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007223:Infant; D041943:Infant Formula; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D009711:Nucleotides / Q000008:administration & dosage*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009711:Nucleotides