title: Effect of fish oil on levels of R- and S-enantiomers of 5-, 12-, and 15-hydroxyeicosatetraenoic acids in mouse colonic mucosa.
abstract: The balance of putative pro- and antiinflammatory lipoxygenase (LOX)-derived S-hydroxyeicosatetraenoic acids (S-HETEs) in colon mucosa is a potential target for modulating colon cancer risk and progression. The biological effects of S-HETEs and R-hydroxyeicosatetraenoic acids (produced by distinct pathways) may differ, but levels of these compounds in the colon are unknown. The objective of this study was to develop chiral methods to characterize hydroxyeicosatetraenoic (HETE) enantiomers in colonic mucosa and evaluate the effects of fish oil on HETE formation. C57BL/6 mice (COX-1 null, COX-2 null, wild-type) were fed a diet supplemented with either olive oil or menhaden oil for 11 wk, and R-/S-HETEs in colonic mucosa were quantified by chiral LC-MS/MS. The R-enantiomer comprised 60-72% of 5-HETE, 18-58% of 15-HETE, and 1-16% of 12-HETE in colonic mucosa, suggesting that non-LOX sources contribute to HETE profiles. Fish oil reduced levels of both R- and S-HETEs, and increased the preponderance of the R-enantiomers (particularly 12- and 15-HETEs). There was apparent shunting of arachidonic acid to 12-/15-LOX in the COX-1 null animals. This is the first report of the enantiomeric composition of HETEs in the colon in vivo and shows large effects of fish oil in the normal colon.
authors.affiliation: Department of Family Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan 48197, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Neilson
authors.forename: Jianwei
authors.initials: J
authors.lastname: Ren
authors.forename: Yu H
authors.initials: YH
authors.lastname: Hong
authors.forename: Ananda
authors.initials: A
authors.lastname: Sen
authors.forename: William L
authors.initials: WL
authors.lastname: Smith
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.forename: Zora
authors.initials: Z
authors.lastname: Djuric
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013237:Stereoisomerism
chemical_list: D005227:Fatty Acids; D005395:Fish Oils; D006893:Hydroxyeicosatetraenoic Acids; D008565:Membrane Proteins; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse