Metabolism of leukotrienes is impaired in hepatocytes from rats with thioacetamide-induced liver cirrhosis.

It is likely that the hepatocellular metabolism of potent mediators of inflammation is impaired in chronic liver injury. Therefore, in this study the degradation of the leukotrienes LTC4, LTE4 and LTB4 was investigated in isolated liver parenchymal cells (LPC) from rats with thioacetamide-induced macronodular liver cirrhosis or after bile duct ligation. The degradation of LTE4 as well as the formation of N-acetyl-LTE4 was significantly delayed in LPC from macronodular cirrhotic rats but not in those from bile duct-ligated rats. LPC from macronodular cirrhotic rats eliminated LTC4 at the same rate as isolated hepatocytes from control animals. The rate of LTB4 degradation was significantly decreased by 35% in LPC from macronodular cirrhotic rats. Furthermore, the rate of LTB4 hydroxylation was significantly lower by 50% in microsomes isolated from hepatocytes of macronodular cirrhotic rats than in those from controls. In summary, one may conclude that the N-acetylation reaction of LTE4 and the hydroxylation reaction of LTB4 is impaired in LPC from rats with thioacetamide-induced macronodular cirrhosis.