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Guinea pig epidermis generates putative anti-inflammatory metabolites from fish oil polyunsaturated fatty acids

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Lipids

Abstract

Clinical studies have indicated that dietary fish oil may have therapeutic value in the treatment of psoriasis, a hyperproliferative, inflammatory skin disorder characterized by elevated LTB4. To evolve a possible mechanism for these beneficial effects, we determined the metabolic fate of fish oil derived n-3 fatty acids in the skin. Specifically, we incubated guinea pig epidermal enzyme preparations with [3H]eicosapentaenoic acid (20∶5n−3) and [14C]docosahexaenoic acid (22∶6n−3). Analyses of the radiometabolites revealed the transformation of these n−3 fatty acids into n−6 lipoxygenase (arachidonate 15-lipoxygenase) products: 15-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHE), respectively. Since 15-lipoxygenase products have been suggested as possible endogenous inhibitors of 5-lipoxygenase (an enzyme which catalyzes the formation of LTB4) we tested the ability of 15-HEPE and 17-HDHEin vitro to inhibit the activity of the 5-lipoxygenase. Incubations of these metabolites with enzyme preparations from rat basophilic leukemia (RBL-1) cells demonstrated that 15-HEPE (IC50=28 μM) and 17-HDHE (IC50=20 μM) are respectively potent inhibitors of RBL-I-5-lipoxygenase. The inhibitory potential of these fish oil metabolites provides a possible mechanism by which fish oil might act to decrease local cutaneous levels of LTB4, and thereby alleviate psoriatic symptoms.

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Abbreviations

PUFA:

polyunsaturated fatty acid

LTB4 :

leukotriene B4

HODE:

hydroxyoctadecadienoic acid

HETrE:

hydroxyeicosatrienoic acid

HETE:

hydroxyeicosatetraenoic acid

HEPE:

hydroxyeicosapentaenoic acid

HDHE:

hydroxydocosahexaenoic acid

GC/MS:

gas chromatography/mass spectrometry

RP-HPLC:

reverse phase-high performance liquid chromatography

GSH:

reduced glutahhione

BSTFA:

N,O-bis(trimethylsilyl) trifluoroacetaminde

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Authors and Affiliations

  1. Department of Dermatology, TB 192, School of Medicine, University of California, 95616, Davis, CA

    Craig C. Miller, Ronald Y. Yamaguchi & Vincent A. Ziboh

Authors
  1. Craig C. Miller
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  2. Ronald Y. Yamaguchi
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  3. Vincent A. Ziboh
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Miller, C.C., Yamaguchi, R.Y. & Ziboh, V.A. Guinea pig epidermis generates putative anti-inflammatory metabolites from fish oil polyunsaturated fatty acids. Lipids 24, 998–1003 (1989). https://doi.org/10.1007/BF02544068

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  • DOI: https://doi.org/10.1007/BF02544068

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