Suppression of cytokine production by thromboxane A2 inhibitor in liver ischemia.
OBJECTIVE
The possible involvement of a thromboxane (TX) A2 inhibitor, sodium ogzarel (SO) was investigated in the regulation of tumor necrosis factor (TNF) alpha and interleukin (IL)1-alpha in liver ischemia and reperfusion (I/R) injury.


METHODS
Rat livers were subjected to 90 min of total hepatic ischemia. Five minutes before the ischemia insult, 10 mg/kg of SO was administered intravenously (SO group); control animals received normal saline solution (NS group). Plasma levels of aspartate aminotransferase (AST), hyaluronic acid (HA), TNF-alpha, IL-1 alpha and three plastanoids, 6-keto prostaglandin (PG) F1 alpha, PGE2 and TXB2, were measured before ischemia insult and 5, 60 and 120 min after reperfusion. Parts of the left lateral lobe were taken for measurement of adenosine nucleotides and histological examination. The cumulative survival rates for the first 10 days after I/R injury were examined for each group. SO was administered at various doses (0.3-30 mg/kg) and TXB2, TNF-alpha and IL-1 alpha were measured.


RESULTS
Significant differences were recognized between the plasma AST, HA, TXB2, TNF-alpha, IL-1 alpha and energy charge levels, the degree of liver necrosis and survival rates of the two groups. Dose-dependent inhibition by SO of the production of TXB2, TNF-alpha and IL-1 alpha was observed.


CONCLUSIONS
Regulation of TNF-alpha and IL-1 alpha by SO is possibly associated with the hepatoprotective effect of SO.
Sugawara
Y
Y
Second Department of Surgery, Faculty of Medicine, University of Tokyo, Japan.
Harihara
Y
Y
Takayama
T
T
Makuuchi
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D006820:Hyaluronic Acid / Q000097:blood; D007375:Interleukin-1 / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000227:Adenine Nucleotides; D007375:Interleukin-1; D008689:Methacrylates; D014409:Tumor Necrosis Factor-alpha; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases; D015232:Dinoprostone; C034364:ozagrel