ArticleArchives of toxicology2022
Farnesoid X receptor (FXR) agonists induce hepatocellular apoptosis and impair hepatic functions via FXR/SHP pathway.
Article in Archives of toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Pepper Leaf Extracts Alleviate HFD-Induced Metabolic Disorders via Microbiota-Driven Intestinal Barrier Repair and Bile Acid Reprogramming.Nutrients · 2026Article
- 4-Hydroxyphenanthrene exacerbates obesity by altering gut microbiota and bile acid metabolism.Nature communications · 2026Article
- Regulation of bile acids homeostasis: a feasible and versatile way to treat or diagnose liver disorders.Frontiers in nutrition · 2026Review
- Chronic Hepatitis B: Current Management and Future Directions.Diseases (Basel, Switzerland) · 2025Review
- Emerging role of bile acids in colorectal liver metastasis: From molecular mechanism to clinical significance (Review).International journal of oncology · 2025Review
- Overview of mechanism of electroacupuncture pretreatment for prevention and treatment of cardiovascular and cerebrovascular diseases.CNS neuroscience & therapeutics · 2024Review
- Review of current and new drugs for the treatment of metabolic-associated fatty liver disease.Hepatology international · 2024Review
- Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy.International journal of molecular sciences · 2023Review
- Ivermectin Attenuates CClInternational journal of molecular sciences · 2022Article
- The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity.International journal of molecular sciences · 2022Review
- Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis.International journal of molecular sciences · 2022Review
- The contribution of the gut-liver axis to the immune signaling pathway of NAFLD.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Farnesoid X receptor (FXR) plays an indispensable role in liver homeostasis and has been a promising drug target for hepatic diseases. However, the concerns of undesired biological actions limit the clinical applications of FXR agonists. To reveal the intrinsic mechanism of FXR agonist-induce hepatotoxicity, two typical FXR agonists with different structures (obeticholic acid (OCA) and Px-102) were investigated in the present study. By detecting MMP, ROS, and ATP and analyzing the fate of cells, we found that both OCA and Px-102 reduced the mitochondrial function of hepatocytes and promoted cell apoptosis. Gene ablation or inhibition of FXR or SHP ameliorated the cytotoxicities of OCA and Px-102, which indicated the adverse actions of FXR/SHP activation including down-regulation of phosphorylation of PI3K/AKT and functional hepatic genes. The dose-related injurious effects of OCA (10 mg/kg and 30 mg/kg) and Px-102 (5 mg/kg and 15 mg/kg) on the liver were confirmed on a high-fat diet mouse model. The decrease of hepatocyte-specific genes and augmenter of liver regeneration in the liver caused by OCA or Px-102 suggested an imbalance of liver regeneration and a disruption of hepatic functions. Exploration of intestinally biased FXR agonists or combination of FXR agonist with apoptosis inhibitor may be more beneficial strategies for liver diseases.
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