TY - JOUR
T1 - A new drug delivery system targeting ileal epithelial cells induced electrogenic sodium absorption
T2 - Possible promotion of intestinal adaptation
AU - Haneda, Sho
AU - Fukushima, Kouhei
AU - Funayama, Yuji
AU - Shibata, Chikashi
AU - Takahashi, Ken Ichi
AU - Tabata, Yasuhiko
AU - Sasaki, Iwao
N1 - Funding Information:
This work was supported by Grant-in-Aid for Scientific research 10557118, and 14657295 from the Ministry of Education, Science and Culture of Japan (to K. Fukushima), Kanae Foundation (to K. Fukushima). S.Haneda.K.Fukushima(*).Y.Funayama.C.Shibata. K.-I. Takahashi.I. Sasaki Department of Surgery, Tohoku University, Graduate School of Medicine, 1-1, Seiryomachi, Aobaku, Sendai 980-8574, Japan e-mail: kouhei@surg1.med.tohoku.ac.jp
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Aldosterone
KW - Intestinal adaptation
KW - Total proctocolectomy
KW - Ulcerative colitis
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U2 - 10.1007/s11605-007-0145-8
DO - 10.1007/s11605-007-0145-8
M3 - Article
C2 - 17468916
AN - SCOPUS:34247628033
VL - 11
SP - 568
EP - 577
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
SN - 1091-255X
IS - 5
ER -