8-11-12-trihydroxy-5-9-14-eicosatrienoic-acid and 10-hydroxy-11-12-epoxyeicosa-5-8-14-trienoic-acid

We recently found that normal human epidermis produces relatively high amounts of hepoxilins and trioxilins in vitro. Therefore, the aim of this study was to demonstrate the presence of these compounds in psoriatic lesions. Extracts from scales of patients with chronic stable plaque psoriasis were analyzed by a combination of high performance liquid chromatography and gas chromatography-mass spectrometry techniques. We found that the levels of hepoxilin B3 were more than 16-fold higher in psoriatic scales than in normal epidermis (3.2+/-2.3 and < 0.2 ng per mg, respectively), whereas hepoxilin A3 was not detected in any sample. Trioxilins were semiquantitated and referred to 12-hydroxyeicosatetraenoic acid, ratios of trioxilins A3 and B3 12-hydroxyeicosatetraenoic acid in psoriatic lesions were 0.65+/-0.23 and 0.32+/-0.28, respectively, and they were not detected in normal epidermis. The presence of a great amount of trioxilin A3 strongly suggests that hepoxilin A3 was present in psoriatic lesions and it was totally degraded to trioxilin A3 during the analysis procedure. Our results demonstrate that hepoxilins and trioxilins are produced by human skin in vivo and that the levels of these compounds are increased in psoriasis. The reported biologic activities of hepoxilins indicate that they could amplify and maintain the inflammatory response. Our results reinforce the idea that these compounds could play a role as mediators in the inflammatory response in skin, particularly in psoriasis.

Topics: 8,11,14-Eicosatrienoic Acid; Chromatography, High Pressure Liquid; Epidermis; Gas Chromatography-Mass Spectrometry; Humans; Hydroxyeicosatetraenoic Acids; Psoriasis; Reference Values

We have identified three main antiplatelet constituents, namely adenosine, allicin and paraffinic polysulfides in both garlic and onion. Adenosine and allicin both inhibited platelet aggregation without affecting cyclooxygenase and lipoxygenase metabolites of arachidonic acid. The trisulfides inhibited platelet aggregation as well as thromboxane synthesis along with induction of new lipoxygenase metabolites. The data indicate that the observed in vivo antiplatelet effects of ingesting onion and garlic are attributable more to the adenosine than to the allicin and paraffinic polysulfide constituents.

Topics: 8,11,14-Eicosatrienoic Acid; Adenosine; Allium; Animals; Arachidonic Acid; Arachidonic Acids; Disulfides; Female; Garlic; Humans; Lipoxygenase; Male; Plants, Medicinal; Platelet Aggregation Inhibitors; Rabbits; Sulfides; Sulfinic Acids; Thromboxane B2

Arachidonic acid and 12-hydroperoxyeicosa-5,8, 10, 14-tetraenoic acid are converted by a 0-30% ammonium sulfate fraction (Fraction A) of the high speed supernatant of rat lung into two hydroxy epoxides (EH-1 and EH-2) which have been purified by high performance liquid chromatography. These hydroxy epoxides are converted quantitatively into two triols (10,11,12- from EH-1 and 8,11,12- from EH-2) by a 30-50% ammonium sulfate fraction (Fraction B) of the high speed supernatant. We propose the structures, 8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid (EH-2) and 10-hydroxy-11,12-epoxyeicosa-5,8,14-trienoic acids (EH-1) for these intermediates on the basis of mass spectral interpretation of several derivatives including the lithium aluminum hydride reduction product of both natural and 18Oxygenated derivatives.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Epoxy Compounds; Ethers, Cyclic; Fatty Acids, Unsaturated; Isomerism; Lung; Male; Mass Spectrometry; Rats; Rats, Inbred Strains; Tritium