Inhibition of inducible nitric oxide synthase prevents hepatic, but not pulmonary, injury following ischemia-reperfusion of rat liver.
The aim of this study was to investigate the contribution of inducible nitric oxide synthase (iNOS)-derived nitric oxide on the liver and lung injury following hepatic ischemia-reperfusion (I/R) using a novel and potent iNOS inhibitor, ONO-1714. Rats were subjected to 90 min of partial hepatic ischemia followed by 3, 6, 12, and 24 hr of reperfusion. Expression of iNOS mRNA peaked at 3 hr of reperfusion in the liver and lung. Plasma nitric oxide levels were increased fourfold at 24 hr of reperfusion and plasma ALT was increased, reaching a peak at 12 hr of reperfusion; both were significantly inhibited by ONO-1714. Histological examination revealed extensive liver damage, whereas this was not seen in the ONO-1714 group. Lung injury was not significantly changed in groups with versus without ONO-1714. Nitrotyrosine expression was seen in regions similar to those of the histological injuries of the liver, while this staining was absent in the ONO-1714 group. These data show that generation of peroxynitrite could be involved in the pathogenesis of liver injury but not lung injury after hepatic I/R. Inhibition of iNOS could be applied for attenuation of liver injury following hepatic I/R.
Takamatsu
Yuji
Y
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shimada
Kazuo
K
Yamaguchi
Koji
K
Kuroki
Syoji
S
Chijiiwa
Kazuo
K
Tanaka
Masao
M
D000578:Amidines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications / Q000628:therapy; D008099:Liver / Q000098:blood supply*; D008107:Liver Diseases / Q000517:prevention & control*; D008171:Lung Diseases / Q000517:prevention & control*; D008297:Male; D008969:Molecular Sequence Data; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects* / Q000378:metabolism; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015424:Reperfusion / Q000379:methods; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
C407360:7-chloro-3-imino-5-methyl-2-azabicyclo(4.1.0)heptane; D000578:Amidines; D006574:Heterocyclic Compounds, 2-Ring; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II