ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Alteration of Bile Acid and Cholesterol Biosynthesis and Transport by Perfluorononanoic Acid (PFNA) in Mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis.Environmental health perspectives · 2022Pooled it
- Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Article
- Perfluorononanoic Acid (PFNA) Exacerbates Atopic Dermatitis by Inducing Inflammation in Mice.Toxics · 2025Article
- Effects of PFAS on human liver transporters: implications for health outcomes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Distinct bile acid alterations in response to a single administration of PFOA and PFDA in mice.Toxicology · 2024Article
- Article
- 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
- Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease.Frontiers in public health · 2023Review
- Perfluorinated Carboxylic Acids with Increasing Carbon Chain Lengths Upregulate Amino Acid Transporters and Modulate Compensatory Response of Xenobiotic Transporters in HepaRG Cells.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Predicting the effects of per- and polyfluoroalkyl substance mixtures on peroxisome proliferator-activated receptor alpha activity in vitro.Toxicology · 2022Article
- Perfluorooctanoic acid activates multiple nuclear receptor pathways and skews expression of genes regulating cholesterol homeostasis in liver of humanized PPARα mice fed an American diet.Toxicology and applied pharmacology · 2020Article
- Gut Microbiota, Peroxisome Proliferator-Activated Receptors, and Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2020Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Perfluorochemicals produce hepatotoxic effects via activation of peroxisome proliferator-activated receptor alpha (PPARα) and constitutive androstane receptor (CAR) nuclear receptors in animals. Bile formation is one major liver function. But it remains unknown whether perfluorochemicals alter metabolism of bile acids (BAs) in liver. The present study was designed to determine the impact of perfluorononanoic acid (PFNA) on BA and cholesterol homeostasis in mice. A single dose of PFNA (0.1 mmol/kg) was intraperitoneally administered to adult male wild-type (WT), PPARα-null, and CAR-null mice. PFNA caused cholestasis in the WT mice, indicated by increased serum alanine aminotransferase, hyperbilirubinemia, elevated BA concentrations in mouse serum, and appearance of bile plugs in mouse liver. In addition, PFNA decreased total and some individual BAs in mouse liver. PFNA increased the concentrations of total and taurine-conjugated, as well as some individual BAs in the serum of WT and CAR-null mice but not in PPARα-null mice, indicating a PPARα-dependent mechanism. PFNA decreased mRNA expression of most BA-related transporters (sodium-taurocholate cotransporting polypeptide, organic anion transporting polypeptide [Oatp]1a1, Oatp1b2, and bile salt export pump) and BA biosynthetic enzymes (Cyp7a1, 7b1, 8b1, and 27a1) in mouse liver, but increased mRNA expression of some efflux transporters (breast cancer resistance protein, multidrug resistance transporter 2, multidrug resistance-associated protein [Mrp] 2, Mrp3, and Mrp4), primarily via a PPARα-dependent mechanism. Moreover, PFNA increased free and total cholesterol in mouse liver but not in mouse serum. Furthermore, PFNA increased mRNA expression of sterol transporters, namely Abca1, g1, g5/g8, and steroidogenic acute regulatory protein via PPARα. In conclusion, PFNA produced cholestasis in mouse liver, and the activation of PPARα plays a central role in regulating BA and cholesterol metabolism and transport in mouse serum and liver.
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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.