Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial
•RvE1 and 15-epi-LXA4 were not detectable (>20 pg/ml).•18-HEPE and 15-HETE were present in ng/ml amounts in plasma.•EPA treatment was associated with increased levels of 18-HEPE.•18-HEPE levels did not predict colorectal polyp risk reduction by EPA. Aspirin and eicosapentaenoic acid (EPA) have co...
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| container_title | Prostaglandins, leukotrienes and essential fatty acids |
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| creator | Fuller, H. Race, A.D. Fenton, H. Burke, L. Downing, A. Williams, E.A. Rees, C.J. Brown, L.C. Loadman, P.M. Hull, M.A. |
| description | •RvE1 and 15-epi-LXA4 were not detectable (>20 pg/ml).•18-HEPE and 15-HETE were present in ng/ml amounts in plasma.•EPA treatment was associated with increased levels of 18-HEPE.•18-HEPE levels did not predict colorectal polyp risk reduction by EPA.
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.
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.
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 |
| doi_str_mv | 10.1016/j.plefa.2023.102570 |
| format | Article |
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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.
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.
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.
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.</description><identifier>ISSN: 0952-3278</identifier><identifier>EISSN: 1532-2823</identifier><identifier>DOI: 10.1016/j.plefa.2023.102570</identifier><identifier>PMID: 37003144</identifier><language>eng</language><publisher>Scotland: Elsevier Ltd</publisher><subject>Aspirin - therapeutic use ; Colorectal cancer ; Colorectal polyp ; Eicosapentaenoic Acid - therapeutic use ; HEPE ; HETE ; Humans ; Lipoxin ; Lipoxins ; Mucous Membrane ; Oxylipin ; Oxylipins ; Resolvin</subject><ispartof>Prostaglandins, leukotrienes and essential fatty acids, 2023-05, Vol.192, p.102570-102570, Article 102570</ispartof><rights>2023 The Author(s)</rights><rights>Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-be437e7b758cf3d755368af3b066020c81cfb1d6e40881be4d33c79e9aff08eb3</citedby><cites>FETCH-LOGICAL-c404t-be437e7b758cf3d755368af3b066020c81cfb1d6e40881be4d33c79e9aff08eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S095232782300039X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37003144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fuller, H.</creatorcontrib><creatorcontrib>Race, A.D.</creatorcontrib><creatorcontrib>Fenton, H.</creatorcontrib><creatorcontrib>Burke, L.</creatorcontrib><creatorcontrib>Downing, A.</creatorcontrib><creatorcontrib>Williams, E.A.</creatorcontrib><creatorcontrib>Rees, C.J.</creatorcontrib><creatorcontrib>Brown, L.C.</creatorcontrib><creatorcontrib>Loadman, P.M.</creatorcontrib><creatorcontrib>Hull, M.A.</creatorcontrib><title>Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial</title><title>Prostaglandins, leukotrienes and essential fatty acids</title><addtitle>Prostaglandins Leukot Essent Fatty Acids</addtitle><description>•RvE1 and 15-epi-LXA4 were not detectable (>20 pg/ml).•18-HEPE and 15-HETE were present in ng/ml amounts in plasma.•EPA treatment was associated with increased levels of 18-HEPE.•18-HEPE levels did not predict colorectal polyp risk reduction by EPA.
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.
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.
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.
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.</description><subject>Aspirin - therapeutic use</subject><subject>Colorectal cancer</subject><subject>Colorectal polyp</subject><subject>Eicosapentaenoic Acid - therapeutic use</subject><subject>HEPE</subject><subject>HETE</subject><subject>Humans</subject><subject>Lipoxin</subject><subject>Lipoxins</subject><subject>Mucous Membrane</subject><subject>Oxylipin</subject><subject>Oxylipins</subject><subject>Resolvin</subject><issn>0952-3278</issn><issn>1532-2823</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi0EokvhCZCQj1yyjO0kdg4cqooCUqVygLPl2BPwyomNnVTslSfH2y0cOc1o5vtnpI-Q1wz2DFj_7rBPASez58BFnfBOwhOyY53gDVdcPCU7GDreCC7VBXlRygEAOGPtc3IhJIBgbbsjv78EU2ZDzeJoRruaQOfNxlJr_HUMPvmFBrzHUKjbsl--U1OSr81DAv0JTbisBpfoLTXWO7pmNOtch7Ri6w-kBa9u7qKjKYZjoinXe8vqY11mb8JL8mwyoeCrx3pJvt18-Hr9qbm9-_j5-uq2sS20azNiKyTKUXbKTsLJrhO9MpMYoe-Bg1XMTiNzPbagFKu0E8LKAQczTaBwFJfk7fluyvHnhmXVsy8WQzALxq1oLgcx1ChTFRVn1OZYSsZJp-xnk4-agT7J1wf9IF-f5Ouz_Jp68_hgG2d0_zJ_bVfg_RmoOvHeY9bFelwsOn9yr130_33wB6lumQs</recordid><startdate>202305</startdate><enddate>202305</enddate><creator>Fuller, H.</creator><creator>Race, A.D.</creator><creator>Fenton, H.</creator><creator>Burke, L.</creator><creator>Downing, A.</creator><creator>Williams, E.A.</creator><creator>Rees, C.J.</creator><creator>Brown, L.C.</creator><creator>Loadman, P.M.</creator><creator>Hull, M.A.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202305</creationdate><title>Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial</title><author>Fuller, H. ; Race, A.D. ; Fenton, H. ; Burke, L. ; Downing, A. ; Williams, E.A. ; Rees, C.J. ; Brown, L.C. ; Loadman, P.M. ; Hull, M.A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-be437e7b758cf3d755368af3b066020c81cfb1d6e40881be4d33c79e9aff08eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aspirin - therapeutic use</topic><topic>Colorectal cancer</topic><topic>Colorectal polyp</topic><topic>Eicosapentaenoic Acid - therapeutic use</topic><topic>HEPE</topic><topic>HETE</topic><topic>Humans</topic><topic>Lipoxin</topic><topic>Lipoxins</topic><topic>Mucous Membrane</topic><topic>Oxylipin</topic><topic>Oxylipins</topic><topic>Resolvin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fuller, H.</creatorcontrib><creatorcontrib>Race, A.D.</creatorcontrib><creatorcontrib>Fenton, H.</creatorcontrib><creatorcontrib>Burke, L.</creatorcontrib><creatorcontrib>Downing, A.</creatorcontrib><creatorcontrib>Williams, E.A.</creatorcontrib><creatorcontrib>Rees, C.J.</creatorcontrib><creatorcontrib>Brown, L.C.</creatorcontrib><creatorcontrib>Loadman, P.M.</creatorcontrib><creatorcontrib>Hull, M.A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Prostaglandins, leukotrienes and essential fatty acids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fuller, H.</au><au>Race, A.D.</au><au>Fenton, H.</au><au>Burke, L.</au><au>Downing, A.</au><au>Williams, E.A.</au><au>Rees, C.J.</au><au>Brown, L.C.</au><au>Loadman, P.M.</au><au>Hull, M.A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial</atitle><jtitle>Prostaglandins, leukotrienes and essential fatty acids</jtitle><addtitle>Prostaglandins Leukot Essent Fatty Acids</addtitle><date>2023-05</date><risdate>2023</risdate><volume>192</volume><spage>102570</spage><epage>102570</epage><pages>102570-102570</pages><artnum>102570</artnum><issn>0952-3278</issn><eissn>1532-2823</eissn><abstract>•RvE1 and 15-epi-LXA4 were not detectable (>20 pg/ml).•18-HEPE and 15-HETE were present in ng/ml amounts in plasma.•EPA treatment was associated with increased levels of 18-HEPE.•18-HEPE levels did not predict colorectal polyp risk reduction by EPA.
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.
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.
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.
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.</abstract><cop>Scotland</cop><pub>Elsevier Ltd</pub><pmid>37003144</pmid><doi>10.1016/j.plefa.2023.102570</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Prostaglandins, leukotrienes and essential fatty acids, 2023-05, Vol.192, p.102570-102570, Article 102570 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aspirin - therapeutic use Colorectal cancer Colorectal polyp Eicosapentaenoic Acid - therapeutic use HEPE HETE Humans Lipoxin Lipoxins Mucous Membrane Oxylipin Oxylipins Resolvin |
| title | Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial |
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