ArticleArchives of toxicology2014
Gemfibrozil disrupts lysophosphatidylcholine and bile acid homeostasis via PPARα and its relevance to hepatotoxicity.
Article in Archives of toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Intestinal metabolomics analysis reveals lysophosphatidylcholine is the key regulatory metabolite in mouse models of necrotizing enterocolitis.Scientific reports · 2025Article
- Comparison of phenotypic and transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and Ppara-null mouse livers.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Robust hierarchical co-clustering for exploring toxicogenomic biomarkers and their chemical regulators.Scientific reports · 2025Article
- Review
- Assessment of the mode of action underlying development of liver lesions in mice following oral exposure to HFPO-DA and relevance to humans.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Molecular Responses of Daphnids to Chronic Exposures to Pharmaceuticals.International journal of molecular sciences · 2023Article
- Toxicity ofFrontiers in pharmacology · 2022Article
- Predicting Target Genes of San-Huang-Chai-Zhu Formula in Treating ANIT-Induced Acute Intrahepatic Cholestasis Rat Model via Bioinformatics Analysis Combined with Experimental Validation.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Epigallocatechin Gallate During Dietary Restriction - Potential Mechanisms of Enhanced Liver Injury.Frontiers in pharmacology · 2020Article
- The Effects of New Selective PPARJournal of diabetes research · 2020Article
- Hepatocyte peroxisome proliferator-activated receptor α regulates bile acid synthesis and transport.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Metabolomics of Aurantio-Obtusin-Induced Hepatotoxicity in Rats for Discovery of Potential Biomarkers.Molecules (Basel, Switzerland) · 2019Article
- Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression.Advanced pharmaceutical bulletin · 2018Article
- PPARα Mediates the Hepatoprotective Effects of Nutmeg.Journal of proteome research · 2018Article
- Targeted Metabolomics Reveals a Protective Role for Basal PPARα in Cholestasis Induced by α-Naphthylisothiocyanate.Journal of proteome research · 2018Article
- Inhibition of JNK signalling mediates PPARα-dependent protection against intrahepatic cholestasis by fenofibrate.British journal of pharmacology · 2017Article
- Peroxisome Proliferator-Activated Receptor α Activation Suppresses Cytochrome P450 Induction Potential in Mice Treated with Gemfibrozil.Basic & clinical pharmacology & toxicology · 2017Article
- Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity.Archives of toxicology · 2017Article
- Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression.Toxicology and applied pharmacology · 2016Article
- Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Gemfibrozil, a ligand of peroxisome proliferator-activated receptor α (PPARα), is one of the most widely prescribed anti-dyslipidemia fibrate drugs. Among the adverse reactions observed with gemfibrozil are alterations in liver function, cholestatic jaundice, and cholelithiasis. However, the mechanisms underlying these toxicities are poorly understood. In this study, wild-type and Ppara-null mice were dosed with a gemfibrozil-containing diet for 14 days. Ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics and traditional approaches were used to assess the mechanism of gemfibrozil-induced hepatotoxicity. Unsupervised multivariate data analysis revealed four lysophosphatidylcholine components in wild-type mice that varied more dramatically than those in Ppara-null mice. Targeted metabolomics revealed taurocholic acid and tauro-α-muricholic acid/tauro-β-muricholic acid were significantly increased in wild-type mice, but not in Ppara-null mice. In addition to the above perturbations in metabolite homeostasis, phenotypic alterations in the liver were identified. Hepatic genes involved in metabolism and transportation of lysophosphatidylcholine and bile acid compounds were differentially regulated between wild-type and Ppara-null mice, in agreement with the observed downstream metabolic alterations. These data suggest that PPARα mediates gemfibrozil-induced hepatotoxicity in part by disrupting phospholipid and bile acid homeostasis.
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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.