The effects of cyclooxygenase (COX)-2 inhibition on ischemia-reperfusion injury in liver transplantation.
OBJECTIVE
Our objective was to evaluate whether COX-2 inhibition with FK3311, a selective cyclooxygenase (COX)-2 inhibitor, improves transplanted liver function.


METHODS
Inbred male Lewis rats weighing 200-260 g were used. The donor liver was perfused with cold University of Wisconsin (UW) solution and then stored in the same solution at 4 degrees C for 18 hr. After the preservation period, orthotopic liver transplantation was performed. Animals were divided into three groups: the control group; the FK low-dose group (1 mg/kg FK3311 i.v. 20 min before reperfusion); and the FK high-dose group (3 mg/kg FK3311 i.v. 20 min before reperfusion). Survival rate, serum GOT and GPT levels, liver tissue blood flow, and serum thromboxane B(2) (TxB(2)) levels were compared among groups.


RESULTS
Survival rate was significantly better (p <. 05) and serum GOT levels 30 min after reperfusion were significantly lower (p <. 05) in the FK high-dose group compared to the other two groups. Four hours after reperfusion, GPT levels and liver tissue flow were significantly (p <. 05) better in the FK high-dose group compared to the control. Both 30 min and 4 hr after reperfusion, serum TxB(2) levels were significantly lower in the FK high-dose group compared to the control (p <. 05).


CONCLUSIONS
COX-2 activity results in deteriorated liver function after I/R injury associated with transplantation, and selective COX-2 inhibition improved liver graft function.
Intensive Care Unit, Gunma University Hospital, Maebashi, Gunma, Japan. koshima@showa.gunma-u.ac.jp
Kiyohiro
K
Oshima
Yoshihiro
Y
Yabata
Daisuke
D
Yoshinari
Izumi
I
Takeyoshi
D000813:Anilides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D019188:Organ Preservation Solutions / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
D000813:Anilides; D052246:Cyclooxygenase 2 Inhibitors; D019188:Organ Preservation Solutions; C085566:FK 3311; D051546:Cyclooxygenase 2