Increased Skin Levels of the Aliamide Palmitoylethanolamide and Other Endogenous Fatty Acid Amides in Dogs with Atopic Dermatitis
Atopic dermatitis (AD) is an itchy chronic skin disease and the second most frequent cutaneous hypersensitivity in dogs. In canine AD, a structurally and functionally defective skin lipid barrier has recently been shown. Several reports that tissue concentrations of endogenous fatty acid amides (FAAs) and endocannabinoids increase in some inflammatory and degenerative disorders have been published. There is evidence that these increases could play an 'autoprotective' role. The purpose of this study was to investigate whether dogs affected with AD exhibited abnormal skin levels of the aliamide palmitoylethanolamide (PEA) and other FAAs.
Punch biopsy specimens (6 mm) were obtained from normal skin of 5 privately owned dogs without clinical evidence of dermatologic disease and from the lesional skin of 5 privately owned dogs diagnosed with AD. All dogs were of various breeds. In the AD group and in the control group dogs were between 1.5 and 11, and between 4 and 13 years of age, respectively. Skin biopsy specimens of approximately the same wet weight in both groups (~45 mg), were stored at -80°C until processing. Tissues were homogenized and lipid-containing organic phase was dried down, weighed and pre-purified by open-bed chromatography on silica gel. The levels of PEA and other compounds listed below were evaluated by isotope dilution liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry (LC-APCI-MS): arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl-glycerol (2-AG), oleylethanolamide (OEA). The amounts of both the lipid extracts and the compounds were compared by the Wilcoxon signed-rank test.
The amount of lipid extract, expressed as percent of biopsy tissue weight, was reduced by ~6-fold in the lesional skin of AD dogs, as compared to control dogs (5.79% vs 35.63%, p<0.05). Conversely, the levels of all measured compounds, normalized to the weight of the corresponding lipid extracts, were significantly elevated (p<0.05). The levels of PEA showed the highest increase, being more than 30-fold higher in AD lesional skin than in normal non-atopic skin. The levels of OEA and 2-AG in AD lesional skin were found to be 30- and 14-fold higher than in normal non-atopic skin, respectively. AEA showed the lowest increase (~6-fold) and also the lowest content in bioptic samples from the canine skin. The present data represent the first demonstration of a significant difference in the lipid content and levels of the aliamide PEA and other FAAs / endocannabinoids between the skin of normal dogs and dogs affected with AD.
Partially supported by Innovet Italia S.r.l.