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5-Fluorouracil treatment alters the expression of intestinal transporters in rats
- Source :
- Biopharmaceuticsdrug disposition. 38(9)
- Publication Year :
- 2017
-
Abstract
- 5-Fluorouracil (5-FU), an anticancer drug, causes severe gastrointestinal damage, which may affect the absorption of orally administered drugs including the substrates of intestinal uptake and efflux transporters. This study aimed to investigate quantitatively the effect of 5-FU-induced intestinal damage on the expression of intestinal transporters: P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and peptide transporter 1 (PEPT1) in rats. The rats were treated with 5-FU (30 mg/kg/day, p.o.) for 5 days to induce intestinal damage, and then the upper, middle and lower intestinal segments were removed. The mRNA and protein expression levels of these transporters in each segment were determined using quantitative real-time PCR and Western blotting, respectively. In the 5-FU-treated rats, the protein levels of P-gp and Bcrp in the upper segment were significantly increased to 15- and 2.6-fold of the control, respectively, while those in other segments were unaffected. Pept1 expression was increased by 5-FU in almost all segments. A remarkable increase in P-gp expression was shown, the uptake of digoxin, a P-gp substrate, in each intestinal segment was measured using a rat everted sac. As a result, the uptake of digoxin in the upper segments of 5-FU-treated rats was decreased compared with that of the control. In conclusion, 5-FU-induced intestinal damage was shown to alter the expression of these transporters, especially in the upper intestinal segment, while the characteristics of the influence varied among the transporters. The 5-FU-induced intestinal damage may affect transporter-mediated drug absorption of orally administered drugs in the clinical setting.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Antimetabolites, Antineoplastic
Digoxin
Abcg2
Blotting, Western
Pharmaceutical Science
Administration, Oral
Pharmacology
Biology
Real-Time Polymerase Chain Reaction
Peptide Transporter 1
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
ATP Binding Cassette Transporter, Subfamily G, Member 2
Animals
Pharmacology (medical)
Drug Interactions
ATP Binding Cassette Transporter, Subfamily B, Member 1
Regulation of gene expression
Messenger RNA
Peptide transporter 1
Transporter
General Medicine
Neoplasm Proteins
Rats
Blot
Intestines
030104 developmental biology
Endocrinology
Real-time polymerase chain reaction
Gene Expression Regulation
030220 oncology & carcinogenesis
biology.protein
Fluorouracil
medicine.drug
Subjects
Details
- ISSN :
- 1099081X
- Volume :
- 38
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Biopharmaceuticsdrug disposition
- Accession number :
- edsair.doi.dedup.....518a4eca7834d2d264ff1d9f52c0c3b2