H. Fuller , A.D. Race , H. Fenton , L. Burke , A. Downing , E.A. Williams , C.J. Rees , L.C. Brown , P.M. Loadman , M.A. Hull
{"title":"seAFOod息肉预防试验中阿司匹林和二十碳五烯酸治疗期间的血浆和直肠粘膜氧基化酶水平","authors":"H. Fuller , A.D. Race , H. Fenton , L. Burke , A. Downing , E.A. Williams , C.J. Rees , L.C. Brown , P.M. Loadman , M.A. Hull","doi":"10.1016/j.plefa.2023.102570","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months.</p></div><div><h3>Methods</h3><p>Resolvin (Rv) E1, 15-epi-lipoxin (LX) A<sub>4</sub> and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants.</p></div><div><h3>Results</h3><p>Despite detection of <em>S</em>- and <em>R</em>- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15‑epi-LXA<sub>4</sub> were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21–1.95] ng/ml at baseline <em>versus</em> 0.95 [0.46–4.06] ng/ml at 6 months [<em>P</em><0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (<em>r</em> = 0.82; <em>P</em><0.001), but which do not predict polyp prevention efficacy by EPA or aspirin.</p></div><div><h3>Conclusion</h3><p>Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15‑epi-LXA<sub>4</sub>. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial\",\"authors\":\"H. Fuller , A.D. Race , H. Fenton , L. Burke , A. Downing , E.A. Williams , C.J. Rees , L.C. Brown , P.M. Loadman , M.A. Hull\",\"doi\":\"10.1016/j.plefa.2023.102570\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months.</p></div><div><h3>Methods</h3><p>Resolvin (Rv) E1, 15-epi-lipoxin (LX) A<sub>4</sub> and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants.</p></div><div><h3>Results</h3><p>Despite detection of <em>S</em>- and <em>R</em>- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15‑epi-LXA<sub>4</sub> were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21–1.95] ng/ml at baseline <em>versus</em> 0.95 [0.46–4.06] ng/ml at 6 months [<em>P</em><0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (<em>r</em> = 0.82; <em>P</em><0.001), but which do not predict polyp prevention efficacy by EPA or aspirin.</p></div><div><h3>Conclusion</h3><p>Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15‑epi-LXA<sub>4</sub>. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.</p></div>\",\"PeriodicalId\":94179,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2023-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S095232782300039X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and essential fatty acids","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S095232782300039X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial
Background
Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months.
Methods
Resolvin (Rv) E1, 15-epi-lipoxin (LX) A4 and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants.
Results
Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15‑epi-LXA4 were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21–1.95] ng/ml at baseline versus 0.95 [0.46–4.06] ng/ml at 6 months [P<0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (r = 0.82; P<0.001), but which do not predict polyp prevention efficacy by EPA or aspirin.
Conclusion
Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15‑epi-LXA4. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.