ArticleDrug metabolism and disposition: the biological fate of chemicals2014
Increases in levels of epoxyeicosatrienoic and dihydroxyeicosatrienoic acids (EETs and DHETs) in liver and heart in vivo by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and in hepatic EET:DHET ratios by cotreatment with TCDD and the soluble epoxide hydrolase inhibitor AUDA.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Triazine herbicide prometryn alters epoxide hydrolase activity and increases cytochrome P450 metabolites in murine livers via lipidomic profiling.Scientific reports · 2024Article
- TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function.Scientific reports · 2021Article
- Review
- Carcinogenesis: Failure of resolution of inflammation?Pharmacology & therapeutics · 2021Review
- Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies.The Journal of nutritional biochemistry · 2020Review
- Lipokines and Thermogenesis.Endocrinology · 2019Review
- Transcriptomic analysis of Anabas testudineus and its defensive mechanisms in response to persistent organic pollutants exposure.The Science of the total environment · 2019Article
- Ethanol promotes differentiation of embryonic stem cells through retinoic acid receptor-γ.The Journal of biological chemistry · 2019Article
- Modulation of mitochondrial dysfunction and endoplasmic reticulum stress are key mechanisms for the wide-ranging actions of epoxy fatty acids and soluble epoxide hydrolase inhibitors.Prostaglandins & other lipid mediators · 2017Review
- The role of AHR-inducible cytochrome P450s in metabolism of polyunsaturated fatty acids.Drug metabolism reviews · 2016Review
- 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) Decreases Hepatic and Systemic Ratios of Epoxide to Diol Metabolites of Unsaturated Fatty Acids in Male Rats.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE₂ induced pain model.Toxicology and applied pharmacology · 2015Article
- Article
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4 authors at 1 institution in 1 country.
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Abstract
The environmental toxin and carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) binds and activates the transcription factor aryl hydrocarbon receptor (AHR), inducing CYP1 family cytochrome P450 enzymes. CYP1A2 and its avian ortholog CYP1A5 are highly active arachidonic acid epoxygenases. Epoxygenases metabolize arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs) and selected monohydroxyeicosatetraenoic acids (HETEs). EETs can be further metabolized by epoxide hydrolases to dihydroxyeicosatrienoic acids (DHETs). As P450-arachidonic acid metabolites affect vasoregulation, responses to ischemia, inflammation, and metabolic disorders, identification of their production in vivo is needed to understand their contribution to biologic effects of TCDD and other AHR activators. Here we report use of an acetonitrile-based extraction procedure that markedly increased the yield of arachidonic acid products by lipidomic analysis over a standard solid-phase extraction protocol. We show that TCDD increased all four EETs (5,6-, 8,9-, 11,12-, and 14,15-), their corresponding DHETs, and 18- and 20-HETE in liver in vivo and increased 5,6-EET, the four DHETs, and 18-HETE in heart, in a chick embryo model. As the chick embryo heart lacks arachidonic acid-metabolizing activity, the latter findings suggest that arachidonic acid metabolites may travel from their site of production to a distal organ, i.e., heart. To determine if the TCDD-arachidonic acid-metabolite profile could be altered pharmacologically, chick embryos were treated with TCDD and the soluble epoxide hydrolase inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA). Cotreatment with AUDA increased hepatic EET-to-DHET ratios, indicating that the in vivo profile of P450-arachidonic acid metabolites can be modified for potential therapeutic intervention.
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