ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Chronic exposure to rifaximin causes hepatic steatosis in pregnane X receptor-humanized mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- A Universal Plasticizer Alkylsulfonic Phenyl Ester Activates Pregnane X Receptor to Increase Intestinal Cholesterol Uptake.International journal of molecular sciences · 2026Article
- Physiological Functions and Pathological Roles of PXR.Journal of the Endocrine Society · 2025Review
- Development and hepatotoxicity of rifamycin derivatives.Expert opinion on drug metabolism & toxicology · 2025Review
- Rifaximin prophylaxis in MASLD‑hepatocellular carcinoma: Lessons from a negative animal model.Biomedical reports · 2025Article
- An insight into carcinogenic activity and molecular mechanisms of Bis(2-ethylhexyl) phthalate.Frontiers in toxicology · 2024Article
- Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor.Frontiers in endocrinology · 2024Article
- Review
- Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in Mice.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Atypical functions of xenobiotic receptors in lipid and glucose metabolism.Medical review (2021) · 2022Review
- Article
- Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice.Acta pharmaceutica Sinica. B · 2022Article
- Review
- Rifaximin Ameliorates Non-alcoholic Steatohepatitis in Mice Through Regulating gut Microbiome-Related Bile Acids.Frontiers in pharmacology · 2022Article
- Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice.Environmental health perspectives · 2021Article
- Article
- Targeting the pregnane X receptor using microbial metabolite mimicry.EMBO molecular medicine · 2020Article
- Nuclear receptors and liver disease: Summary of the 2017 basic research symposium.Hepatology communications · 2018Review
- 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
- Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view.Environmental epigenetics · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Rifaximin, a nonsystemic antibiotic that exhibits low gastrointestinal absorption, is a potent agonist of human pregnane X receptor (PXR), which contributes to its therapeutic efficacy in inflammatory bowel disease. To investigate the effects of long-term administration of rifaximin on the liver, PXR-humanized mice were administered rifaximin for 6 months; wild-type and Pxr-null mice were treated in parallel as controls. Histological analysis revealed time-dependent intense hepatocellular fatty degeneration and increased hepatic triglycerides in PXR-humanized mice and not in wild-type and Pxr-null mice. After long-term treatment, PXR target genes were induced in small intestine and liver, with significant up-regulation in the expression of hepatic genes related to triglyceride synthesis and lipid accumulation. However, no significant hepatic accumulation of rifaximin was found, even after 6 months of treatment, in PXR-humanized mice. Genes in the small intestine that are involved in the uptake of fatty acids and triglycerides were induced along with increased triglyceride accumulation in intestinal epithelial cells of PXR-humanized mice; this was not observed in wild-type and Pxr-null mice. These findings suggest that long-term administration of rifaximin could lead to PXR-dependent hepatocellular fatty degeneration as a result of activation of genes involved in lipid uptake, thus indicating a potential adverse effect of rifaximin on liver function after long-term exposure.
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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.