The effect of arachidonic acid metabolite inhibitors on liver injury in endotoxin shock, with special reference to the role of polymorphonuclear leukocytes (PMNs)

Abstract

To elucidate the effect of arachidonic acid metabolite inhibitors on liver injury in endotoxin shock with special reference to the role of polymorphonuclear leukocytes (PMNs), we pretreated rats with three kinds of arachidonic acid metabolite inhibitors (hydrocortisone, Hy; AA-861, AA; indomethacin, In) in our rat model of endotoxin shock. We examined plasma GOT and GLDH levels, O2- production by PMNs, the phagocytic activity of PMNs, the cytotoxicity of PMNs to liver cells, the histological changes in the liver, and so on, and compared the three groups Hy, AA and In with the ET (endotoxin) group, which was only infused with endotoxin. 1) Plasma GOT and GLDH levels were significantly lower in the Hy and AA groups than in the ET group, but there was no significant change in the In group in comparison with the ET group. 2) The amount of O2- production by PMNs was significantly lower in the Hy group than in the ET group when there was no stimulation. When PMNs were stimulated by PMA, O2- production was significantly lower in the other three groups than in the ET group. 3) The phagocytic activity of PMNs was significantly lower in the other three groups than in the ET group. 4) The cytotoxic activity of PMNs to liver cells, which was seen in the ET group, was completely inhibited in the Hy and AA groups, but was only slightly prevented in the In group. 5) Concerning histological changes in the liver, there were remarkable improvements in the Hy and AA groups as compared with the ET group, but the findings in the In group were similar to those in the ET group.(ABSTRACT TRUNCATED AT 250 WORDS)