Role of granulocyte elastase in ischemia/reperfusion injury of rat liver.
OBJECTIVE
To investigate the role of granulocyte elastase in ischemia/reperfusion injury of liver, the effect of ONO-5046, a granulocyte elastase inhibitor, was examined in ischemia/reperfusion-induced liver injury in rats.


METHODS
Prospective, randomized, controlled study.


METHODS
Research laboratory at a university medical center.


METHODS
Male Wistar rats, weighing 220 to 280 g.


METHODS
Animals receiving continuous intravenous infusion of ONO-5046 (50 mg/kg/hr) were subjected to hepatic ischemia/reperfusion. Hepatic damage was evaluated by effects on bile formation capacity, plasma clearance of indocyanine green, and serum aminotransferase concentrations after ischemia/reperfusion.


RESULTS
Hepatic dysfunction, observed after 60 mins of ischemia/reperfusion, led to a reduction in bile flow and to a decrease in the plasma clearance of indocyanine green. These indicators of hepatic dysfunction were prevented, to a large extent, by administration of ONO-5046. Serum concentrations of aminotransferases increased after hepatic ischemia/reperfusion, peaking at 12 hrs of reperfusion. Increases in serum concentrations of aminotransferases were significantly inhibited by ONO-5046.


CONCLUSIONS
Granulocyte elastase derived from activated leukocytes may play a critical role in hepatic dysfunction and the subsequent hepatic injury induced by ischemia/reperfusion.
Kushimoto
S
S
Department of Laboratory Medicine, Kumamoto University Medical School, Japan.
Okajima
K
K
Uchiba
M
M
Murakami
K
K
Harada
N
N
Okabe
H
H
Takatsuki
K
K
D000818:Animals; D001646:Bile / Q000187:drug effects; D004396:Coloring Agents / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007208:Indocyanine Green / Q000378:metabolism; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000502:physiology*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000637:Transaminases / Q000097:blood
D004396:Coloring Agents; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D000637:Transaminases; D019272:Leukocyte Elastase; D007208:Indocyanine Green; D005998:Glycine