ArticleThe Biochemical journal2005
Pregnenolone-16alpha-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms.
Article in The Biochemical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
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Who cites it
46 citing papers in PubMed, 89 citations in OpenAlex.
- Impact of Mlkl or Ripk3 deletion on age-associated liver inflammation, metabolic health, and lifespan.GeroScience · 2025Article
- Insights of direct and indirect regulation of PXR through phosphorylation in fatty liver disease.Molecular pharmacology · 2025Review
- Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy.Kidney international reports · 2024Review
- Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/β-catenin signaling.Acta pharmacologica Sinica · 2023Article
- Potential for cardiac toxicity with methylimidazolium ionic liquids.Ecotoxicology and environmental safety · 2023Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- The Role of Vitamin K in Cholestatic Liver Disease.Nutrients · 2021Review
- The methylimidazolium ionic liquid M8OI is detectable in human sera and is subject to biliary excretion in perfused human liver.Toxicology · 2021Article
- Prevention of D-GalN/LPS-induced ALI by 18β-glycyrrhetinic acid through PXR-mediated inhibition of autophagy degradation.Cell death & disease · 2021Article
- Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis-Roles as Putative Treatment Targets?Biomedicines · 2021Review
- Renal injury and hepatic effects from the methylimidazolium ionic liquid M8OI in mouse.Ecotoxicology and environmental safety · 2020Article
- Changes in the gut microbiota of mice orally exposed to methylimidazolium ionic liquids.PloS one · 2020Article
- Identification of a xenobiotic as a potential environmental trigger in primary biliary cholangitis.Journal of hepatology · 2018Article
- Pregnane X receptor promotes ethanol-induced hepatosteatosis in mice.The Journal of biological chemistry · 2018Article
- Targeting nuclear receptors for the treatment of fatty liver disease.Pharmacology & therapeutics · 2017Review
- B-13 progenitor-derived hepatocytes (B-13/H cells) model lipid dysregulation in response to drugs and chemicals.Toxicology · 2017Article
- Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse.Toxicology letters · 2017Article
- Environmental Xenoestrogens Super-Activate a Variant Murine ER Beta in Cholangiocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies.Nature reviews. Drug discovery · 2016Review
- Progenitor-derived hepatocyte-like (B-13/H) cells metabolise 1'-hydroxyestragole to a genotoxic species via a SULT2B1-dependent mechanism.Toxicology letters · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The effect of liver growth stimulation [using the rodent PXR (pregnane X receptor) activator PCN (pregnenolone-16alpha-carbonitrile)] in rats chronically treated with carbon tetrachloride to cause repeated hepatocyte necrosis and liver fibrogenesis was examined. PCN did not inhibit the hepatotoxicity of carbon tetrachloride. However, transdifferentiation of hepatic stellate cells and the extent of fibrosis caused by carbon tetrachloride treatment was significantly inhibited by PCN in vivo. In vitro, PCN directly inhibited hepatic stellate cell transdifferentiation to a profibrogenic phenotype, although the cells did not express the PXR (in contrast with hepatocytes), suggesting that PCN acts independently of the PXR. Mice with a functionally disrupted PXR gene (PXR-/-) did not respond to the antifibrogenic effects of PCN, in contrast with wild-type (PXR+/+) mice, demonstrating an antifibrogenic role for the PXR in vivo. However, PCN inhibited the transdifferentiation of PXR-/--derived mouse hepatic stellate cells in vitro, confirming that there is also a PXR-independent antifibrogenic effect of PCN through a direct interaction with hepatic stellate cells. These data suggest that the PXR is antifibrogenic in rodents in vivo and that a PXR-independent target for PXR activators exists in hepatic stellate cells that also functions to inhibit fibrosis.
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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.