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

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 (20:5 n-3) and [14C]docosahexaenoic acid (22:6 n-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-HDHE in 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 microM) and 17-HDHE (IC50 = 25 microM) 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.

• Authors: C Miller, R Y Yamaguchi, V A Ziboh
• Journal: Lipids (Lipids) Vol. 24 Issue 12 Pg. 998-1003 (Dec 1989) ISSN: 0024-4201 [Print] United States
• PMID: 2559281 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Fatty Acids, Unsaturated
• Fish Oils
• Lipoxygenase Inhibitors
• Leukotriene B4
• Docosahexaenoic Acids
• 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid
• 15-hydroxy-5,8,11,13,17-eicosapentaenoic acid
• Eicosapentaenoic Acid

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal
• Chromatography, High Pressure Liquid
• Docosahexaenoic Acids (pharmacology)
• Eicosapentaenoic Acid (analogs & derivatives, biosynthesis, pharmacology)
• Epidermis (enzymology, metabolism)
• Fatty Acids, Unsaturated (metabolism, pharmacology)
• Fish Oils (metabolism, pharmacology)
• Guinea Pigs
• Leukotriene B4 (biosynthesis)
• Lipoxygenase Inhibitors
• Male
• Psoriasis (drug therapy)
• Tumor Cells, Cultured