ArticleJournal of cellular and molecular medicine2011
Bile acids decrease intracellular bilirubin levels in the cholestatic liver: implications for bile acid-mediated oxidative stress.
Article in Journal of cellular and molecular medicine, 2011. 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, 46 citations in OpenAlex.
- Bilirubin Metabolism Does Not Influence Serum Bile Acid Profiles According to LC-MS: A Human Case-Control Study.International journal of molecular sciences · 2025Article
- Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Common pathogenesis of early and late preeclampsia: evidence from recurrences and review of the literature.Archives of gynecology and obstetrics · 2024Review
- Impact of Intermittent Fasting and Dietary Restriction on Redox State, Energetic Metabolism, and Liver Injury in Common Bile Duct Ligation Model.Antioxidants (Basel, Switzerland) · 2024Article
- The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease.Seminars in liver disease · 2023Review
- Combined effect of hydrogen sulfide and mesenchymal stem cells on mitigating liver fibrosis induced by bile duct ligation: Role of anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-fibrotic biomarkers.Iranian journal of basic medical sciences · 2021Article
- Ileal bile acid transporter inhibition as an anticholestatic therapeutic target in biliary atresia and other cholestatic disorders.Hepatology international · 2020Review
- Hyperbilirubinemia in Gunn Rats is Associated with Decreased Inflammatory Response in LPS-Mediated Systemic Inflammation.International journal of molecular sciences · 2019Article
- Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study.PloS one · 2019Article
- HYCO-3, a dual CO-releaser/Nrf2 activator, reduces tissue inflammation in mice challenged with lipopolysaccharide.Redox biology · 2019Article
- Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition.Oxidative medicine and cellular longevity · 2018Article
- Systems pharmacology modeling of drug-induced hyperbilirubinemia: Differentiating hepatotoxicity and inhibition of enzymes/transporters.Clinical pharmacology and therapeutics · 2017Article
- Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Protective effect of heme oxygenase induction in ethinylestradiol-induced cholestasis.Journal of cellular and molecular medicine · 2015Article
- Protective Effect of Calculus Bovis Sativus on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- Liver metabolomics reveals increased oxidative stress and fibrogenic potential in gfrp transgenic mice in response to ionizing radiation.Journal of proteome research · 2014Article
- Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease.Clinical and experimental gastroenterology · 2014Review
- Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome.Free radical biology & medicine · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High plasma concentrations of bile acids (BA) and bilirubin are hallmarks of cholestasis. BA are implicated in the pathogenesis of cholestatic liver damage through mechanisms involving oxidative stress, whereas bilirubin is a strong antioxidant. We evaluated the roles of bilirubin and BA on mediating oxidative stress in rats following bile duct ligation (BDL). Adult female Wistar and Gunn rats intraperitoneally anaesthetized with ketamine and xylazine underwent BDL or sham operation. Cholestatic markers, antioxidant capacity, lipid peroxidation and heme oxygenase (HO) activity were determined in plasma and/or liver tissue 5 days after surgery. HepG2-rNtcp cells were used for in vitro experiments. Plasma bilirubin levels in control and BDL animals positively correlated with plasma antioxidant capacity. Peroxyl radical scavenging capacity was significantly higher in the plasma of BDL Wistar rats (210 ± 12%, P < 0.0001) compared to controls, but not in the liver tissues. Furthermore after BDL, lipid peroxidation in the livers increased (179 ± 37%, P < 0.01), whereas liver HO activity significantly decreased to 61% of control levels (P < 0.001). Addition of taurocholic acid (TCA, ≥ 50 μmol/l) to liver homogenates increased lipid peroxidation (P < 0.01) in Wistar, but not in Gunn rats or after the addition of bilirubin. In HepG2-rNtcp cells, TCA decreased both HO activity and intracellular bilirubin levels. We conclude that even though plasma bilirubin is a marker of cholestasis and hepatocyte dysfunction, it is also an endogenous antioxidant, which may counteract the pro-oxidative effects of BA in circulation. However, in an animal model of obstructive cholestasis, we found that BA compromise intracellular bilirubin levels making hepatocytes more susceptible to oxidative damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.