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

Richter, Lothar; Hesselbarth, Norbert; Eitner, K; Schubert, K. R.; Bosseckert, H; Krell, Herbert

doi:10.1016/s0168-8278(96)80245-5

Cited by 15 publications

(12 citation statements)

References 23 publications

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“…This is first report to demonstrate the clinical significance of cysteinyl LTs in human bile associated with bacterial cholangitis, which is the most frequent and critical complication in obstructive jaundice. 19,20 In earlier studies of the analysis of cysteinyl LTs in bile in patients with obstructive jaundice, the concentrations of endogenous LTC 4 , LTD 4 , and LTE 4 2 h after drainage averaged approximately 28, 7, and 17 nM, respectively, 18 values which are considerably higher than our determinations. Especially, we found LTC 4 only in patients with bacterial cholangitis (Fig.…”

Section: Discussioncontrasting

confidence: 65%

“…15,16,18 We developed a two-step RP-HPLC for purification of human bile, which enabled us to quantify endogenous cysteinyl LTs by subsequent RIA. In our method, the final recovery of each LT was relatively low, but the absolute amount of endogenous LT in each 1-min fraction determined by RIA showed a sharp peak corresponding to that of the standard substance (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In view of the metabolism and biological actions of cysteinyl LTs, it is of interest to determine the biliary cysteinyl LTs in patients with obstructive jaundice whose hepatobiliary elimination of cysteinyl LTs is strongly impaired. Recently, increased biliary secretion of cysteinyl LTs has been demonstrated in patients with obstructive jaundice, 18 but information was lacking on the relationship of biliary cysteinyl LTs to clinical features, including bacterial cholangitis, which is the most frequent and critical complication associated with endotoxemia in bile duct obstruction. 19,20 The aim of this study was to quantify the endogenous cysteinyl LTs in human bile by two-step reversed-phase high-performance liquid chromatography (RP-HPLC) and subsequent radioimmunoassay (RIA), and to explore the significance of biliary cysteinyl LTs associated with clinical features and laboratory findings in patients with obstructive jaundice.…”

Section: Introductionmentioning

confidence: 99%

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Cysteinyl leukotrienes in the bile of patients with obstructive jaundice

Uemura

Kojima

Buchholz

et al. 2002

Journal of Gastroenterology

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Section: Discussioncontrasting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cysteinyl leukotrienes in the bile of patients with obstructive jaundice

Uemura

Kojima

Buchholz

et al. 2002

Journal of Gastroenterology

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“…There is evidence that the diseased liver of patients with cholestatic liver disease is exposed to oxidative stress associated with lipid peroxidation [5,6]. In addition, it has been shown that inflammation contributes to development of cholestatic liver injury in humans [7][8][9]. Increased production of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-a) and IL-6, has also been implicated [10].…”

Section: Introductionmentioning

confidence: 99%

Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis

et al. 2006

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Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n=10) or BDL (n=20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P<0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P<0.001). All of these changes were significantly attenuated (P<0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.

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“…Inflammation is known to contribute to the development of cholestatic liver injury from biliary obstruction in patients [2,3]. Experimental studies have determined that a pro-inflammatory response was initiated by endotoxin or LPS treatment in animal models with biliary obstruction following an increase in cytokine production of TNF-α, IL-1β, and IL-6 [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Activity of Dehydroandrographolide by TLR4/NF-κB Signaling Pathway Inhibition in Bile Duct-Ligated Mice

Weng

Chi

Xie

et al. 2018

Cell Physiol Biochem

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Background/Aims: Clinically, biliary obstruction is often accompanied by progressive inflammation. Dehydroandrographolide (DA) possesses anti-inflammatory properties. However, the anti-inflammatory activities of DA in cholestatic liver injury remain unclear. Methods: Mice were administered with DA by intraperitoneal injection after bile duct ligation (BDL) on day 1. Then mice were subjected to an ileocecal vein injection of lipopolysaccharide (LPS). Liver function markers, histology, pro-inflammatory cytokine levels, NF-κB activation and fibrosis formation were evaluated in BDL mice with LPS. LPS binding to primary Kupffer cells was examined by high-content cytometers. Results: DA was shown to greatly lower initially higher than normal levels of alanine aminotransferase (ALT) and total bilirubin (TBIL) in the serum and liver of BDL mice with LPS. DA exerted hepatic protective effects that were also confirmed by prolonged survival of BDL mice with LPS. Liver histopathology showed reduced inflammatory cellular infiltration, bile duct proliferation, and biliary necrosis with DA treatment. Furthermore, DA reduced the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in liver tissue and plasma and showed decreased NF-κB activation in BDL mice with LPS. DA could prevent LPS binding to primary Kupffer cells in the normal liver and BDL mice liver. DA also suppressed LPS-stimulated inflammatory responses by blocking the interaction between LPS and TLR4 in primary Kupffer cells and human LX-2 cells, thereby inhibiting NF-κB activation. Conclusion: DA inhibition of inflammation against liver damage following BDL with LPS may be a promising agent for the treatment of cholestatic liver injury.

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

Cited by 15 publications

References 23 publications

Cysteinyl leukotrienes in the bile of patients with obstructive jaundice

Cysteinyl leukotrienes in the bile of patients with obstructive jaundice

Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis

Anti-Inflammatory Activity of Dehydroandrographolide by TLR4/NF-κB Signaling Pathway Inhibition in Bile Duct-Ligated Mice

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