ArticleGut2003
Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat.
Article in Gut, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 69 citations in OpenAlex.
- Resveratrol Alleviates Arsenic-Induced Liver Fibrosis in Rats by Correcting SIRT1-Mediated Disorder of Hepatic Bile Acid Metabolism.International journal of molecular sciences · 2026Article
- Transcriptional and Post-Transcriptional Anticholestatic Mechanisms of Obeticholic Acid in Lipopolysaccharide-Induced Cholestasis.Pharmaceutics · 2025Article
- Secondary bile acids and the biliary epithelia: The good and the bad.World journal of gastroenterology · 2023Review
- Simultaneous determination of perfluoroalkyl substances and bile acids in human serum using ultra-high-performance liquid chromatography-tandem mass spectrometry.Analytical and bioanalytical chemistry · 2020Article
- Ursodeoxycholate Restores Biliary Excretion of Methotrexate in Rats with Ethinyl Estradiol Induced-Cholestasis by Restoring Canalicular Mrp2 Expression.International journal of molecular sciences · 2018Article
- Protein kinase Cδ protects against bile acid apoptosis by suppressing proapoptotic JNK and BIM pathways in human and rat hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Role of protein kinase C isoforms in bile formation and cholestasis.Hepatology (Baltimore, Md.) · 2014Review
- Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease.International journal of experimental pathology · 2014Article
- Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI.CPT: pharmacometrics & systems pharmacology · 2014Article
- Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations.Molecular aspects of medicine · 2014Review
- A C-terminal tyrosine-based motif in the bile salt export pump directs clathrin-dependent endocytosis.Hepatology (Baltimore, Md.) · 2012Article
- INTRACELLULAR SIGNALING BY BILE ACIDS.Journal of bio-science · 2012Article
- Sequential activation of classic PKC and estrogen receptor α is involved in estradiol 17ß-D-glucuronide-induced cholestasis.PloS one · 2012Article
- ERK1/2 and p38 MAPKs are complementarily involved in estradiol 17ß-D-glucuronide-induced cholestasis: crosstalk with cPKC and PI3K.PloS one · 2012Article
- Prevention of estradiol 17beta-D-glucuronide-induced canalicular transporter internalization by hormonal modulation of cAMP in rat hepatocytes.Molecular biology of the cell · 2011Article
- The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease.Seminars in liver disease · 2010Review
- PKC{epsilon}-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line.American journal of physiology. Gastrointestinal and liver physiology · 2009Article
- Ca(2+)-dependent protein kinase C isoforms are critical to estradiol 17beta-D-glucuronide-induced cholestasis in the rat.Hepatology (Baltimore, Md.) · 2008Article
- Dynamic localization of hepatocellular transporters in health and disease.World journal of gastroenterology · 2008Review
- Bile acid transporters in health and disease.Xenobiotica; the fate of foreign compounds in biological systems · 2008Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundTaurolithocholate induced cholestasis is a well established model of drug induced cholestasis with potential clinical relevance. This compound impairs bile salt secretion by an as yet unclear mechanism.
aimsTo evaluate which step/s of the hepatocellular bile salt transport are impaired by taurolithocholate, focusing on changes in localisation of the canalicular bile salt transporter, Bsep, as a potential pathomechanism.
methodsThe steps in bile salt hepatic transport were evaluated in rats in vivo by performing pharmacokinetic analysis of (14)C taurocholate plasma disappearance. Bsep transport activity was determined by assessing secretion of (14)C taurocholate and cholyl-lysylfluorescein in vivo and in isolated rat hepatocyte couplets (IRHC), respectively. Localisation of Bsep and F-actin were assessed both in vivo and in IRHC by specific fluorescent staining.
resultsIn vivo pharmacokinetic studies revealed that taurolithocholate (3 micro mol/100 g body weight) diminished by 58% canalicular excretion and increased by 96% plasma reflux of (14)C taurocholate. Analysis of confocal images showed that taurolithocholate induced internalisation of Bsep into a cytosolic vesicular compartment, without affecting F-actin cytoskeletal organisation. These effects were reproduced in IRHC exposed to taurolithocholate (2.5 micro M). Preadministration of dibutyryl-cAMP, which counteracts taurolithocholate induced impairment in bile salt secretory function in IRHC, restored Bsep localisation in this model. Furthermore, when preadministered in vivo, dibutyryl-cAMP accelerated recovery of both bile flow and bile salt output, and improved by 106% the cumulative output of (14)C taurocholate.
conclusionsTaurolithocholate impairs bile salt secretion at the canalicular level. Bsep internalisation may be a causal factor which can be prevented by dibutyryl-cAMP.
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Registered trials
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