SUPPRESSION OF CYTOKINE PRODUCTION BY THROMBOXANE A2 INHIBITOR IN LIVER ISCHEMIA

BAGKGROUND/AIMS: The possible involvement of a thromboxane (TX) A(2) i nhibitor, sodium ogzarel (SO) was investigated in the regulation of tu mor necrosis factor (TNF) alpha and interleukin (IL)1-alpha in liver i schemia and reperfusion (I/R) injury. METHODOLOGY: Rat livers were sub jected to 90 min of total hepatic ischemia. Five minutes before the is chemia 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) Fl alpha, PGE(2) and TXB2, were measured before ischemia insult and 5, 60 and 120 min after reperfusion. Parts of the left; lateral lobe were t aken for measurement of adenosine nucleotides and histological examina tion. The cumulative survival rates for the first 10 days after I/R in jury were examined for each group. SO was administered at various dose s (0.3-30 mg/kg) and TXB2, TNF-alpha and IL-1 alpha were measured. RES ULTS: Significant differences were recognized between the plasma AST, HA, TXB2, TNF-alpha, IL-1 alpha and energy charge levels, the degree o f 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 w as observed. CONCLUSIONS: Regulation of TNF-alpha and IL-1 alpha by SO is possibly associated with the hepatoprotective effect of SO.