The effects of a cyclooxygenase-2 inhibitor, FK3311, on total hepatic ischemia-reperfusion injury of the rat
Kobayashi, M.; Takeyoshi, I.; Kurabayashi, M.; Matsumoto, K.; Morishita, Y.
Hepato-Gastroenterology 54(74): 522-526
2007
ISSN/ISBN: 0172-6390 PMID: 17523312 Document Number: 606106
Background/Aims: This study was designed to investigate the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the rat liver.Methodology: 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, 1.0mg/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) 132 and 6-ketoprostaglandin (PG) Fl(, (stable metabolites of TxA(2) and PGI(2)) were measured 30 min after reperfusion. The Ever 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 TxB(2) were significantly lower than in the control group. By contrast, the 6-keto-PG F1 alpha 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 TxA(2).