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 liver injury due to bile duct obstruction, we have examined the effects of iloprost, a stable analogue of prostaglandin I2 (PGI2), and UK 38485 (UK), an inhibitor of thromboxane synthetase, on prostaglandin E2 (PGE2) and leukotriene C4(LTC4) in guinea pig liver. 56 male guinea pigs were divided into the following groups: (i) sham operations (SHAM), (ii) bile duct ligated (BDL) group, (iii) guinea pigs given UK (5 micrograms/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct ligation), and (iv) guinea pigs treated with iloprost (ILO) (2 micrograms/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct ligation). Liver damage was assessed by blind quantitation of liver cell necrosis. Bile duct ligation caused an increase in tissue PGE2-like activity and a decrease LTC4-like activity. But the most pronounced elevation of PGE2-like activity was observed in ILO treated group. The LTC4-like activity level improved significantly in the UK-treated BDL group compared with the BDL only and ILO treated animals. Also, UK was found to be beneficial in preventing the liver cell necrosis due to cholestasis. It is concluded that the ratio of PGE2/LTC4 in liver is a valuable marker for cholestatic injury.
Engin
A
A
Department of Surgery, Faculty of Medicine, Gazi University, Beşevler, Ankara, Turkey.
Ercan
Z S
ZS
Memiş
L
L
D000818:Animals; D001652:Bile Ducts; D015415:Biomarkers; D001651:Cholestasis, Extrahepatic / Q000378:metabolism* / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism*; D006168:Guinea Pigs; D016285:Iloprost / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D015415:Biomarkers; D007093:Imidazoles; D017997:Leukotriene C4; C039242:dazmegrel; D013930:Thromboxane-A Synthase; D016285:Iloprost; D015232:Dinoprostone