ArticleFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2021
Increased toxicity and retention of perflourooctane sulfonate (PFOS) in humanized CYP2B6-Transgenic mice compared to Cyp2b-null mice is relieved by a high-fat diet (HFD).
Article in Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2021. 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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 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
- Transcriptomic Insights into Developmental Toxicity of Per- and polyfluoroalkyl Substances (PFAS) inEnvironment & health (Washington, D.C.) · 2026Article
- Perfluorooctane sulfonic acid (PFOS) perturbs skeletal muscle oxidative phosphorylation by a different mechanism than liver.Chemosphere · 2026Article
- Mixtures ofToxics · 2025Article
- Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Review
- Perfluorooctane sulfonate exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding model.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Sexually Dimorphic Effects of CYP2B6 in the Development of Fasting-Mediated Steatosis in Mice: Role of the Oxylipin Products 9-HODE and 9-HOTrE.Biomedicines · 2025Article
- 9-HODE and 9-HOTrE alter mitochondrial metabolism, increase triglycerides, and perturb fatty acid uptake and synthesis associated gene expression in HepG2 cells.Prostaglandins, leukotrienes, and essential fatty acids · 2024Article
- Article
- Replacement per- and polyfluoroalkyl substances (PFAS) are potent modulators of lipogenic and drug metabolizing gene expression signatures in primary human hepatocytes.Toxicology and applied pharmacology · 2022Article
- Human CYP2B6 produces oxylipins from polyunsaturated fatty acids and reduces diet-induced obesity.PloS one · 2022Article
- Age- and Diet-Dependent Changes in Hepatic Lipidomic Profiles of Phospholipids in Male Mice: Age Acceleration in Cyp2b-Null Mice.Journal of lipids · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
PFOS is a persistent, fluorosurfactant used in multiple products. Murine Cyp2b's are induced by PFOS and high-fat diets (HFD) and therefore we hypothesized that human CYP2B6 may alleviate PFOS-induced steatosis. Cyp2b-null and hCYP2B6-Tg mice were treated with 0, 1, or 10 mg/kg/day PFOS by oral gavage for 21-days while provided a chow diet (ND) or HFD. Similar to murine Cyp2b10, CYP2B6 is inducible by PFOS. Furthermore, three ND-fed hCYP2B6-Tg females treated with 10 mg/kg/day PFOS died during the exposure period; neither Cyp2b-null nor HFD-fed mice died. hCYP2B6-Tg mice retained more PFOS in serum and liver than Cyp2b-null mice presumably causing the observed toxicity. In contrast, serum PFOS retention was reduced in the HFD-fed hCYP2B6-Tg mice; the opposite trend observed in HFD-fed Cyp2b-null mice. Hepatotoxicity biomarkers, ALT and ALP, were higher in PFOS-treated mice and repressed by a HFD. However, PFOS combined with a HFD exacerbated steatosis in all mice, especially in the hCYP2B6-Tg mice with significant disruption of key lipid metabolism genes such as Srebp1, Pparg, and Hmgcr. In conclusion, CYP2B6 is induced by PFOS but does not alleviate PFOS toxicity presumably due to increased retention. CYP2B6 protects from PFOS-mediated steatosis in ND-fed mice, but increases steatosis when co-treated with a HFD.
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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 Socratic graph.