Transformation of 15-hydroperoxyeicosapentaenoic acid to lipoxin A5 and B5, mono- and dihydroxyeicosapentaenoic acids by porcine leukocytes.
15-Hydroperoxy[1-14C]eicosapentaenoic acid derived from eicosapentaenoic acid (EPA) was incubated with suspensions of porcine leukocytes. Incubation with porcine leukocytes resulted in the formation of seven dihydroxy compounds, one monohydroxy and one hydroxyepoxy compound. After separation by reverse-phase and straight-phase HPLC, GC/MS analysis revealed that these metabolites were four isomers of 8,15-diHEPEs, two isomers of 14,15-diHEPEs, one isomer of 5,15-diHEPE, 15-HEPE and an epoxyalcohol: 13-hydroxy-14,15-epoxyeicosatetraenoic acid. In addition to the above metabolites, two trihydroxytetraene derivatives were also isolated. GC/MS and ultraviolet spectroscopy identified the two trihydroxypentaene derivatives as 5,6,15-trihydroxy-7,9,11,13,17-eicosapentaenoic acid (lipoxin A5) and 5,14,15-trihydroxy-6,8,10,12,17-eicosapentaenoic acid (lipoxin B5). This study demonstrated that the 15-hydroperoxide of EPA can be actively converted to various hydroxylated products via the 5-, 12- and 15-lipoxygenase as well as epoxyisomerase pathways in the porcine leukocytes.
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism*; D044045:Lipoxins; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D044045:Lipoxins; C044354:lipoxin A5; C044355:lipoxin B5; C044353:15-hydroperoxy-5,8,11,14,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid