The effects of a cyclooxygenase-2 inhibitor, FK3311, on total hepatic ischemia-reperfusion injury of the rat.
OBJECTIVE
This study was designed to investigate the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the rat liver.


METHODS
Male Sprague-Dawley rats were used in this experimental study. Total hepatic ischemia was induced with a clamping portal triad. The animals were divided into two groups: the control group and the FK group, in which FK3311 (FK, 1.0 mg/kg) was administered via the penile vein. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured 2 h after reperfusion, while those of thromboxane (Tx) B2 and 6-ketoprostaglandin (PG) F1alpha (stable metabolites of TxA2 and PGI2) were measured 30 min after reperfusion. The liver tissue blood flow was measured at preischemia, end-ischemia, and 30, 60, 90, and 120 min after reperfusion. The liver tissues obtained from animals at 2h after reperfusion were excised for histopathology.


RESULTS
The serum levels of AST, ALT, and LDH were significantly lower in the FK group than in the control group. Similarly, in the FK group, the serum levels of TxB2 were significantly lower than in the control group. By contrast, the 6-keto-PG F1a levels were not significantly reduced. The liver tissue blood flow at 120 min after reperfusion was significantly higher in the FK group than in the control group. The histopathological study showed that hepatic tissue damage was milder in the FK group than in the control group.


CONCLUSIONS
FK has protective effects on hepatic ischemia-reperfusion injury stemming from the marked inhibition of TxA2.
Kobayashi
Mitsunobu
M
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Takeyoshi
Izumi
I
Kurabayashi
Makoto
M
Matsumoto
Koshi
K
Morishita
Yasuo
Y
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*
D000813:Anilides; D052246:Cyclooxygenase 2 Inhibitors; C085566:FK 3311