Increased biliary secretion of cysteinyl-leukotrienes in human bile duct obstruction

Abstract

Background/Aims: The pathophysiological role of leukotrienes in liver disease is not well understood. Redistribution or enhanced formation in cholestatic states may result in increased hepatic concentrations that are expected to contribute to liver injury. To disclose the potential role of cysteinyl-leukotrienes in chronic liver diseases, we studied biliary and urinary secretion in the model situation of relief of bile duct obstruction. Methods: Concentrations of cysteinyl-leukotrienes were determined in bile and urine of patients with extrahepatic biliary obstruction in the course of therapeutic decompression by endoscopic or transhepatic techniques. Leukotrienes were measured by radioimmunoassay after HPLC separation. Concentrations of bile acids in bile and serum were measured for comparison. Results: Bile collected 2 h after decompression contained high concentrations of leukotrienes (57.5±22 μM). Biliary secretion decreased over 24 h reaching equilibrium values after 48–72 h (2.8±1.7 mM and 6.4±6.6 μM, respectively). Total bile acid concentration in serum followed a similar time course. In contrast, biliary bile acid concentration showed high interindividual variations. Bile contained all leukotriene C4, D4, E4 and Nac-LTE4, but LTC4 was predominant. Urinary leukotriene secretion in cholestasis (199.7 pmol/mmol creatinine) was less than 7% of maximal biliary secretion. It further decreased to 116.4 pmol/mmol creatinine within 72 h. Urine also contained all species of cysteinyl-leukotrienes, but the relative amounts of LTE4 and NAc-LTE4 were higher than in bile. Conclusions: Formation of cysteinyl-leukotrienes is increased in obstructive jaundice resulting in increased urinary excretion before and both biliary and urinary excretion after relief of the obstruction. Predominance of LTC4 suggests that the secreted leukotrienes are newly formed. Increased synthesis and retention of hepatic cysteinyl-leukotrienes may contribute to hepatic and extrahepatic consequences of cholestasis.