Effects of nitric oxide on mucosal barrier dysfunction during early phase of intestinal ischemia/reperfusion.
Ischemia/reperfusion (I/R) injury must be overcome for successful small intestinal transplantation. During intestinal I/R, the expression level of nitric oxide (NO) is increased, and vermiculation of the mucosal tract is induced by NO. Although NO has many beneficial effects on intestinal I/R injury, its role in intestinal I/R injury is controversial. Therefore, in the present study, we examined changes in the tight junctions (TJ) and P-glycoprotein (P-gp) by aminoguanidine (AG), which can be considered a selective inducible NO synthase inhibitor during intestinal I/R, to clarify the effect of NO on mucosal barrier dysfunction during intestinal I/R. A mucosal lesion was induced by intestinal I/R. The protein expression levels of the claudin family organizing TJ and P-gp, were decreased, and their functions were also decreased. Through the inhibition of NO generation by AG in the above mucosal lesion, TJ and P-gp dysfunction was significantly inhibited. NO participated in opening TJ and decreasing P-gp function and expression induced during intestinal I/R. Therefore, it is important to consider the level of NO generation in the ileal mucosa in drug therapy for intestinal I/R injury.
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
Yusuke
Y
Takizawa
Hisanao
H
Kishimoto
Takuya
T
Kitazato
Mikio
M
Tomita
Masahiro
M
Hayashi
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D007413:Intestinal Mucosa / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009569:Nitric Oxide