Biomedical subjects

Makoto Haga

Publications and source records attributed to Makoto Haga.

3 recordsLinked to original sources

PubMed2005

Effectiveness of pirotiodecane, absorption enhancer, on nasal absorption in rabbits.

The absorption enhancing effect of 1-[2-(decylthio) ethyl] azacyclopentan-2-one (Pirotiodecane), on drug permeation across rabbit nasal mucosa was studied. The nasal epithelial mucosa was isolated from rabbit nasal septum and mounted in an Ussing chamber to allow for monitoring of the membrane resistance (Rm), and the permeation of fluorescein isothiocyanate-labeled dextran (FD-4, M.W. 4,400 Da). Treatment with 0.05, 0.1, and 0.2% Pirotiodecane for 60 min decreased Rm, and increased the cumulative amount of FD-4 permeated in a concentration-dependent manner, suggesting that Pirotiodecane possesses passively a disassembly of tight junction to enable the enhanced FD-4 permeation. The remarkable increase in plasma concentration of FD-4 was also observed in intranasal co-administration with 1% Pirotiodecane in rabbits. The Rm was virtually maintained after the removal of Pirotiodecane, although recovery of Rm was not seen. On the other hand, the increase in plasma concentration of FD-4 with intranasal co-administration of 1% Pirotiodecane in rabbits in vivo was not observed in FD-4 administration at 15-60 min after administration of 1% Pirotiodecane alone. It was concluded that Pirotiodecane possesses a relatively short absorption enhancing effect through nasal epithelial.

Administration, Intranasal↗

PubMed2004

Factors affecting glucuronidation activity in Caco-2 cells.

Presystemic intestinal metabolism reduces the intestinal absorption and bioavailability of orally administered drugs. The factors affecting glucuronidation activity in Caco-2 cells seeded in Transwell (4.7 cm(2)) require clarification to establish an in-vitro system to assess intestinal glucuronidation metabolism for novel drug development. alpha-Naphthol (alpha-NA), a substrate for UGT1A6 in Caco-2 cells, has often been used as a model substrate for gluruonidation. alpha-Naphthol glucuronidation activity increased from 7 to 21 culture days after seeding in Transwell and stabilized after 21 days. The higher the passage number of Caco-2 cells, the larger the variance of glucuronidation activity, but apical pH did not significantly influence glucuronidation in the pH range of 5.5 to 7.4. When the passage number ranged from 83 to 159, Km,app was highest at passage number 130. In contrast, Vmax,app increased with the passage number. This indicates that the kinetic parameters for glucuronidation in Caco-2 cells are dependent on the passage number of the cells. These results should be useful for establishing the experimental conditions for Caco-2 cells that predict intestinal glucuronidation activity in vivo.

Area Under Curve↗

PubMed2002

Clarification of the mechanism of structural change induced by reoxygenation following the induction of lipid peroxidation in Caco-2 cell monolayers.

Recently, we established a system for assessing ischemia/reperfusion injury, specifically the opening of tight junctions (TJ), caused by reoxygenation following the induction of lipid peroxidation by tertiary-butylhydroperoxide (t-BuOOH), using the human intestinal epithelial cell line Caco-2 in order to focus on the barrier function of the epithelium independent of the vascular compartment. In the present study, we attempted to identify factors involved in the structural changes induced by reoxygenation using 0.5 mM t-BuOOH in Caco-2 cell monolayers. Glutathione (GSH) and N-acetylcystein, a precursor of GSH, inhibited the opening of TJ evoked by reoxygenation following the induction of lipid peroxidation by 0.5 mM of t-BuOOH. Tiron, as a cell permeable superoxide anion scavenger and deferoxamine, an iron-chelating agent ameliorated the opening in a dose-dependent manner. Also, Tiron suppressed the apical-to-basal and basal-to-apical permeability of the increased Rhodamine123 by reoxygenation in a concentration-dependent manner. These results collectively suggest that superoxide anion and iron ions play an important role or contribute to structural changes such as the opening of TJ induced by reoxygenation following the induction of lipid peroxidation by 0.5 mM t-BuOOH.

Journal Article↗