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RETRACTED ARTICLE: Changes of Absorptive and Secretory Transporting System of (1 → 3) β-D-glucan Based on Efflux Transporter in Indomethacin-induced Rat

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This article was retracted on 14 November 2018

ABSTRACT

Infection and inflammation suppress the expression and activity of several drug transporters in liver. In the intestine, P-glycoprotein (P-gp/MDR1), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) are important barriers to the absorption of many clinically important drugs. The expression and activity of these proteins were examined under inflammation. Drug transport was determined in jejunum and ileum segments isolated from 1.0 mg/kg, 5.0 mg/kg, and 7.5 mg/kg indomethacin-treated or control rats in diffusion chambers. Transport of laminaran, used as a model compound of (1-3) β-D-glucan, was measured for 120 min in the presence or absence of inhibitors. Reverse transcription-polymerase chain reaction was used to measure mRNA levels. Compared with controls, levels of Mdr1a mRNA were significantly decreased in the jejunum and ileum of 7.5 mg/kg indomethacin-treated rats. Both reductions in the basolateral to apical efflux of laminaran and increases in the apical to basolateral influx of laminaran were observed, resulting in significant increases in the apical to basolateral absorption of laminaran in 7.5 mg/kg indomethacin-treated rats. The inhibitory effect of verapamil on laminaran transport was observed in control rats but not in indomethacin-treated rats. Fluorescein isothiocyanate dextran 40,000 permeability, membrane resistance, and claudin-4 mRNA level were not altered, indicating no change in the paracellular pathway. These results indicate that indomethacin-induced inflammation reduces the intestinal expression and activity of P-gp in rats, which elicits corresponding changes in the intestinal transport of laminaran. Hence, inflammatory diseases may impose variability in drug bioavailability through alterations in the intestinal expression and activity of drug transporters.

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Authors and Affiliations

  1. Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Aiko Iida, Shohei Ouchi, Yasuhiko Ito, Yusuke Takizawa, Mikio Tomita & Masahiro Hayashi

  2. Research and Development Department, Research Laboratories, Seikagaku Corporation, 1253 Tateno 3-chome, Higashiyamato, Tokyo, 207-0021, Japan

    Toshio Oda

  3. Technical Support Group, LAL and Biochemicals Marketing Department, Seikagaku Corporation, 6-1 Marunouchi 1-chome, Chiyoda-ku, Tokyo, 101-0042, Japan

    Jun Aketagawa

Authors
  1. Aiko Iida
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  2. Shohei Ouchi
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  3. Toshio Oda
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  4. Jun Aketagawa
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  5. Yasuhiko Ito
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  6. Yusuke Takizawa
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  7. Mikio Tomita
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  8. Masahiro Hayashi
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Corresponding author

Correspondence to Yusuke Takizawa.

Additional information

The Editor-in-Chief has retracted this article [1] based on an investigation by the Ministry of Education, Culture, Sports, Science and Technology, Japan, which found that the article contained overlap with a previously published article by Kalitsky-Szirtes J, et al. [2]. All authors agree with the retraction, but the authors do not agree with the wording of the retraction note. [1] Iida A, Ouchi S, Oda T, et al. Changes of Absorptive and Secretory Transporting System of (1→3) ?-D-glucan Based on Efflux Transporter in Indomethacin-induced Rat. Eur J Drug Metab Pharmacokinet. 2015; 40(1): 29-38. [2] Kalitsky-Szirtes J, Shayeganpour A, Brocks DR, et al. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004; 32(1): 20-7.

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Iida, A., Ouchi, S., Oda, T. et al. RETRACTED ARTICLE: Changes of Absorptive and Secretory Transporting System of (1 → 3) β-D-glucan Based on Efflux Transporter in Indomethacin-induced Rat. Eur J Drug Metab Pharmacokinet 40, 29–38 (2015). https://doi.org/10.1007/s13318-014-0174-0

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  • DOI: https://doi.org/10.1007/s13318-014-0174-0

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