ArticleToxicology and applied pharmacology2010
Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes).
Article in Toxicology and applied pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 44 citations in OpenAlex.
- The Bile Acid Signaling Axis: Deciphering the Roles of FXR and TGR5 in Hepatic Steatosis, Fibrosis, and Cancer.Pharmacology research & perspectives · 2026Review
- Confirmation of high-throughput screening data and novel mechanistic insights into FXR-xenobiotic interactions by orthogonal assays.Current research in toxicology · 2022Article
- FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (Nutrients · 2021Article
- Pharmacophore modeling and virtual screening studies for discovery of novel farnesoid X receptor (FXR) agonists.RSC advances · 2021Article
- Repositioning an Immunomodulatory Drug Vidofludimus as a Farnesoid X Receptor Modulator With Therapeutic Effects on NAFLD.Frontiers in pharmacology · 2020Article
- Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation.Scientific reports · 2017Article
- Hepatic Responses of Juvenile Fundulus heteroclitus from Pollution-adapted and Nonadapted Populations Exposed to Elizabeth River Sediment Extract.Toxicologic pathology · 2016Article
- Selective targeting of nuclear receptor FXR by avermectin analogues with therapeutic effects on nonalcoholic fatty liver disease.Scientific reports · 2015Article
- Protective effects of calycosin against CCl4-induced liver injury with activation of FXR and STAT3 in mice.Pharmaceutical research · 2015Article
- Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor.Scientific reports · 2014Article
- Alcohol disrupts endoplasmic reticulum function and protein secretion in hepatocytes.Alcoholism, clinical and experimental research · 2012Article
- The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species.BMC biochemistry · 2011Article
- Two farnesoid X receptor alpha isoforms in Japanese medaka (Oryzias latipes) are differentially activated in vitro.Aquatic toxicology (Amsterdam, Netherlands) · 2010Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The small freshwater teleost, medaka (Oryzias latipes), has a history of usage in studies of chronic toxicity of liver and biliary system. Recent progress with this model has focused on defining the medaka hepatobiliary system. Here we investigate critical liver function and toxicity by examining the in vivo role and function of the farnesoid X receptor alpha (FXRalpha, NR1H4), a member of the nuclear receptor superfamily that plays an essential role in the regulation of bile acid homeostasis. Quantitative mRNA analysis of medaka FXRalpha demonstrates differential expression of two FXRalpha isoforms designated Fxralpha1 and Fxralpha2, in both free swimming medaka embryos with remaining yolk (eleutheroembryos, EEs) and adults. Activation of medaka Fxralpha in vivo with GW4064 (a strong FXRalpha agonist) resulted in modification of gene expression for defined FXRalpha gene targets including the bile salt export protein, small heterodimer partner, and cytochrome P450 7A1. Histological examination of medaka liver subsequent to GW4064 exposure demonstrated significant lipid accumulation, cellular and organelle alterations in both hepatocytes and biliary epithelial cells of the liver. This report of hepatobiliary injury following GW4064 exposure extends previous investigations of the intrahepatic biliary system in medaka, reveals sensitivity to toxicant exposure, and illustrates the need for added resolution in detection and interpretation of toxic responses in this vertebrate.
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