ArticleActa pharmacologica Sinica2016
Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats.
Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Blood-brain barrier dysfunction in hepatic encephalopathy: pathophysiology, diagnostic assessment and therapeutic perspectives.Metabolic brain disease · 2025Review
- Bile duct ligation impairs visual acuity in rats by ammonia- and bilirubin-induced retinal degeneration.Acta pharmacologica Sinica · 2025Article
- Bile duct ligation-induced cirrhosis does not alter the blood-brain barrier permeability to sucrose in rats.Metabolic brain disease · 2024Article
- Bilirubin and Redox Stress in Age-Related Brain Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice.Nature communications · 2023Article
- Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin.Acta pharmaceutica Sinica. B · 2023Article
- Bile Duct Ligation Impairs Function and Expression of Mrp1 at Rat Blood-Retinal Barrier via Bilirubin-Induced P38 MAPK Pathway Activations.International journal of molecular sciences · 2022Article
- Article
- Bile duct ligation causes opposite impacts on the expression and function of BCRP and P-gp in rat brain partly via affecting membrane expression of ezrin/radixin/moesin proteins.Acta pharmacologica Sinica · 2021Article
- The neurogliovascular unit in hepatic encephalopathy.JHEP reports : innovation in hepatology · 2021Review
- Article
- Bilirubin as a metabolic hormone: the physiological relevance of low levels.American journal of physiology. Endocrinology and metabolism · 2021Review
- Bilirubin Induces Pain Desensitization in Cholestasis by Activating 5-Hydroxytryptamine 3A Receptor in Spinal Cord.Frontiers in cell and developmental biology · 2021Article
- Bile duct ligation enhances AZT CNS toxicity partly by impairing the expression and function of BCRP in rat brain.Acta pharmacologica Sinica · 2020Article
- Prognostic value of preoperative serum bilirubin levels in ovarian cancer.American journal of translational research · 2020Article
- Botryllamide G is an ABCG2 inhibitor that improves lapatinib delivery in mouse brain.Cancer biology & therapy · 2020Article
- Alterations in Expression and Function of ABC Family Transporters at Blood-Brain Barrier under Liver Failure and Their Clinical Significances.Pharmaceutics · 2018Review
- Altered Function and Expression of ABC Transporters at the Blood-Brain Barrier and Increased Brain Distribution of Phenobarbital in Acute Liver Failure Mice.Frontiers in pharmacology · 2018Article
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Authors and funding
11 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
aimLiver failure is associated with dyshomeostasis of efflux transporters at the blood-brain barrier (BBB), which contributes to hepatic encephalopathy. In this study we examined whether breast cancer resistance protein (BCRP), a major efflux transporter at the BBB, was altered during liver failure in rats.
methodsRats underwent bile duct ligation (BDL) surgery, and then were sacrificed after intravenous injection of prazosin on d3, d7 and d14. The brains and blood samples were collected. BCRP function at the BBB was assessed by the brain-to-plasma prazosin concentration ratio; Evans Blue extravasation in the brain tissues was used as an indicator of BBB integrity. The protein levels of BCRP in the brain tissues were detected. Human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) were tested in vitro. In addition, hyperbilirubinemia (HB) was induced in rats by intravenous injection of unconjugated bilirubin (UCB).
resultsBDL rats exhibited progressive decline of liver function and HB from d3 to d14. In the brain tissues of BDL rats, both the function and protein levels of BCRP were progressively decreased, whereas the BBB integrity was intact. Furthermore, BDL rat serum significantly decreased BCRP function and protein levels in HCMEC/D3 cells. Among the abnormally altered components in BDL rat serum tested, UCB (10, 25 μmol/L) dose-dependently inhibit BCRP function and protein levels in HCMEC/D3 cells, whereas 3 bile acids (CDCA, UDCA and DCA) had no effect. Similar results were obtained in MDCK-BCRP cells and in the brains of HB rats. Correlation analysis revealed that UCB levels were negatively correlated with BCRP expression in the brain tissues of BDL rats and HB rats as well as in two types of cells tested in vitro.
conclusionUCB elevation in BDL rats impairs the function and expression of BCRP at the BBB, thus contributing to hepatic encephalopathy.
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