A new drug delivery system targeting ileal epithelial cells induced electrogenic sodium absorption: Possible promotion of intestinal adaptation

Sho Haneda, Kouhei Fukushima, Yuji Funayama, Chikashi Shibata, Ken Ichi Takahashi, Yasuhiko Tabata, Iwao Sasaki

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

We previously demonstrated the induction of the epithelial sodium channel, prostasin, and 11β-hydroxysteroid dehydrogenase type 2 and activation of sodium transport mediated by those molecules in the remnant ileum after total proctocolectomy. The aims of the present study were to develop a new drug delivery system that targets ileal epithelial cells and to enhance local mineralocorticoid action without systemic effects. Orally administered d-aldosterone-containing d,l-lactide/glycolide acid copolymer microspheres are absorbed in the rat terminal ileum and released aldosterone. Blood and terminal ileal tissues were collected 2 weeks after the administration of the microspheres, and the aldosterone concentrations, mRNA, and protein expressions of the above molecules and sodium transport were evaluated. Significantly high levels of tissue aldosterone in the absence of elevated plasma levels were detected in the microspheres-treated rats. Epithelial mRNA and protein expression of the above molecules increased significantly in the microspheres-treated animals. Electrogenic sodium transport in the ileum was enhanced in the microspheres-treated rats. Aldosterone-containing microspheres successfully induced the expression of the above molecules and activated sodium transport in the ileal mucosa, both of which are essential for intestinal adaptation. Pre- and/or postoperative treatment with this drug may compensate for the excessive loss of sodium and water following proctocolectomy.

Original languageEnglish
Pages (from-to)568-577
Number of pages10
JournalJournal of Gastrointestinal Surgery
Volume11
Issue number5
DOIs
Publication statusPublished - 2007 May

Keywords

  • Aldosterone
  • Intestinal adaptation
  • Total proctocolectomy
  • Ulcerative colitis

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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