THE PROTECTIVE EFFECT OF THROMBOXANE SYNTHETASE INHIBITOR UK-38485 AGAINST BILE-DUCT LIGATION INDUCED LIVER-INJURY

In order to elucidate the relation between tissue eicosanoids and live r injury due to bile duct obstruction, we have examined the effects of iloprost, a stable analogue of prostaglandin I-2 (PGI(2)), and UK 384 85 (UK), an inhibitor of thromboxane synthetase, on prostaglandin E(2) (PGE(2)) and leukotriene C-4 (LTC(4)) in guinea pig liver, 56 male gu inea pigs were divided into the following groups: (i) sham operations (SHAM), (ii) bile duct ligated (BDL) group, (iii) guinea pigs given UK (5 mu g/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct ligation), and (iv) guinea pigs treated with iloprost (ILO) (2 mu g/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct l igation). Liver damage was assessed by blind quantitation of liver cel l necrosis. Bile duct ligation caused an increase in tissue PGE(2)-lik e activity and a decrease LTC(2)-like activity. But the most pronounce d elevation of PGE(2) was observed in ILO treated group. The LTC(4)-li ke activity level improved significantly in the UK-treated BDL group c ompared with the BDL only and ILO treated animals. Also, UK was found to be beneficial in preventing the liver cell necrosis due to cholesta sis. It is concluded that the ratio of PGE(2)/LTC(4) in liver is a val uable marker for cholestatic injury.