title: Effect of aminoguanidine on ischemia/reperfusion injury in rat small intestine.
abstract: Ischemia/reperfusion (I/R) injury is induced by reactive oxygen species (ROS). During intestinal I/R, the amount of nitric oxide (NO), which is a ROS, is increased. In this study, we examined the protection against I/R injury by inhibition of NO generation. Wistar/ST rats were exposed to 1 h of ischemia, followed by reperfusion for 4 h. The rats were intravenously injected with 100 mg/kg aminoguanidine (AG), which is a selective inducible NO synthase (iNOS) inhibitor, for 5 min before ischemia. The increase in NO(2)(-) by intestinal I/R was significantly inhibited by AG 1 h after reperfusion. Moreover, the increase in area under curve of 0 to 1 h after reperfusion (AUC(0-1)) of paracellular marker was inhibited. However, 3 h after reperfusion, the survival ratio of rats was significantly decreased in the intestinal I/R condition with AG. The amount of NO(2)(-) and AUC of 3 to 4 h after reperfusion (AUC(3-4)) of paracellular marker in intestinal I/R groups were increased by AG compared with those in the I/R condition without AG 3 h after reperfusion. These data indicated that AG, which was given by single pre-administration, can clearly inhibit intestinal I/R injury 1 h after reperfusion. However, the injury occurs again 3 h after reperfusion and grows worse.
authors: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, Japan.
authors: Yusuke
authors: Y
authors: Takizawa
authors: Takuya
authors: T
authors: Kitazato
authors: Haruka
authors: H
authors: Ishizaka
authors: Naomi
authors: N
authors: Kamiya
authors: Mikio
authors: M
authors: Tomita
authors: Masahiro
authors: M
authors: Hayashi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007421:Intestine, Small / Q000187:drug effects*; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine