8-11-14-eicosatrienoic-acid and Skin-Diseases

Several mediators contribute to postocclusive reactive hyperemia (PORH) of the skin, including sensory nerves and endothelium-derived hyperpolarizing factors. The main objective of our study was to investigate the specific contribution of epoxyeicosatrienoic acids in human skin PORH. Eight healthy volunteers were enrolled in two placebo-controlled experiments. In the first experiment we studied the separate and combined effects of 6.5 mM fluconazole, infused through microdialysis fibers, and lidocaine/prilocaine cream on skin PORH following 5 min arterial occlusion. In the second experiment we studied the separate and combined effects of 6.5 mM fluconazole and 10 mM N(G)-monomethyl-l-arginine (l-NMMA). Skin blood flux was recorded using two-dimensional laser speckle contrast imaging. Maximal cutaneous vascular conductance (CVC(max)) was obtained following 29 mM sodium nitroprusside perfusion. The PORH peak at the placebo site averaged 66 ± 11%CVC(max). Compared with the placebo site, the peak was significantly lower at the fluconazole (47 ± 10%CVC(max); P < 0.001), lidocaine (29 ± 10%CVC(max); P < 0.001), and fluconazole + lidocaine (30 ± 10%CVC(max); P < 0.001) sites. The effect of fluconazole on the area under the curve was more pronounced. In the second experiment, the PORH peak was significantly lower at the fluconazole site, but not at the l-NMMA or combination site, compared with the placebo site. In addition to sensory nerves cytochrome epoxygenase metabolites, putatively epoxyeicosatrienoic acids, play a major role in healthy skin PORH, their role being more important in the time course rather than the peak.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme System; Female; Fluconazole; Humans; Hyperemia; Lidocaine; Male; NG-Nitroarginine Methyl Ester; Nitroprusside; Regional Blood Flow; Sensory Receptor Cells; Skin; Skin Diseases

Polyunsaturated fatty acids (PUFAs) are known to play important roles in various physiological and pathological processes. Recent studies have shown that some omega-3 (omega-3) PUFAs, such as eicosapentaenoic acid (EPA) and dodecahexaenoic acid (DHA), have protective effects on acute and chronic UV-induced changes. However, the effects of other omega-3 PUFAs including 11,14,17-eicosatrienoic acid (20:3) (ETA) on UV-induced skin damages are poorly understood. In this study, we investigated the cutaneous photoprotective effects of ETA in hairless mice in vivo. Female HR-1 hairless mice were topically treated with vehicle (ethanol:polyethylene glycol=30:70) only, 0.1% ETA, or 1% ETA once a day for 3 successive days after one time UV irradiation (200 mJ/cm(2)) on dorsal skins. Skin biopsy was carried out on the fourth day (72 hr after UV irradiation). We found that topical treatment with ETA attenuated UV-induced epidermal and dermal thickness and infiltration of inflammatory cells, and impairment of skin barrier function. In addition, ETA suppressed the expression of IL-1beta, COX-2, and MMP-13 induced by UV irradiation. Our results show that the topical application of ETA protects against UV-induced skin damage in hairless mice and suggest that ETA can be a potential agent for preventing and/or treating UV-induced inflammation and photoaging.

Topics: 8,11,14-Eicosatrienoic Acid; Administration, Topical; Animals; Cyclooxygenase 2; Female; Interleukin-1beta; Matrix Metalloproteinase 13; Mice; Mice, Hairless; Radiation-Protective Agents; Skin; Skin Diseases; Ultraviolet Rays

The present studies have demonstrated that topical application of a low concentration of eicosa-5,8,11-trienoic acid (a 20:3,n9 fatty acid previously reported to inhibit competitively the activity of the sheep vesicular cyclooxygenase) to skin of normal fed hairless mice produced severe scaly dermatosis which is characterized by marked hyperplasia and acanthosis of the epidermal layer. The precise mechanism of this induction of scaly dermatosis is presently unclear. It is nonetheless interesting that the treatment of skin with similar concentrations of other unsaturated fatty acids produced no visible or histologic effects. Furthermore, endogenous levels of arachidonic acid in epidermal phospholipid and triglyceride fractions were shown to increase significantly (p < 0.01) in skin treated with the 20:3,n9 fatty acid while the endogenous level of PGE2 in the same tissue decreased markedly. This latter observation is consistent at least in part, with a previous report from this laboratory in which the 20:3,n9 fatty acid inhibited in vitro the activity of the sheep vesicular cyclooxygenase (the rate limiting enzyme in the transformation of arachidonic acid into the prostaglandin endoperoxides) although the increase in arachidonic acid may also reflect an increased incorporation of this fatty acid into the epidermal lipids by the hyperproliferative tissue. Evaluation of the proliferative status of 20:3,n9 fatty acid-treated skin showed a significant increase (p < 0.01) in labeling and mitotic indices. The use of this potentially endogenous fatty acid may be a useful tool for further investigations of hyperproliferative skin diseases where dietary deficiency of essential fatty acids does not exist.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acids; Cell Division; Disease Models, Animal; Fatty Acids, Unsaturated; Female; Lipids; Mice; Mice, Nude; Prostaglandins E; Skin; Skin Diseases