title: Characteristics of reversible absorption-enhancing effect of sodium nitroprusside in rat small intestine.
abstract: Nitric oxide (NO) donors increase the permeability of water-soluble compounds with neither loss of cell viability nor lactate dehydrogenase release. In addition, the rectal absorption of insulin has been reported to be remarkably enhanced in the presence of NO donors such as 1-Hydroxy-3-(3-aminopropyl)-3-isopropyltriazene 2-oxide (NOC5) and N-Ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC12). In this study, we examined the effect of sodium nitroprusside (SNP), which is used in clinical situations as a vasodilator, as a model NO donor on the ileal mucosa of rats. We used an in situ closed loop method in rat ileum to study changes in the permeability of fluorescein isothiocyanate dextran 4000 (FD-4) as a paracellular marker. The effect of SNP (1 and 10mg/kg) on the protein expression level of the claudin family was examined by Western blotting. The membrane permeation of FD-4 was increased but no mucosal lesion was observed upon the administration of SNP. Moreover, the protein expression level of the claudin family was not changed by the administration of SNP. When SNP was removed 2h after its administration, no significant change in the membrane permeation of FD-4 was observed. Moreover, no decrease of ileal membrane resistance or disruption of membrane structure was observed. The absorption-enhancing effect of SNP was associated with low injury and low toxicity. The reversibility of the effect of SNP was observed. Consequently, it was shown that SNP can be a useful absorption enhancer.
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan. takizawa@toyaku.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takizawa
authors.forename: Hisanao
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitazato
authors.forename: Haruka
authors.initials: H
authors.lastname: Ishizaka
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamiya
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Mikio
authors.initials: M
authors.lastname: Tomita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D057167:Claudins / Q000378:metabolism; D007082:Ileum / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D057167:Claudins; D020030:Nitric Oxide Donors; D009573:Nitrites; D010743:Phospholipids; D009599:Nitroprusside
keywords: Absorption enhancer; Claudin family; Nitric oxide; Paracellular marker; Sodium nitroprusside