Inhibitory effect of topical Adelmidrol on antigen-induced skin wheal and mast cell behavior in a canine model of allergic dermatitis

Abstract

BackgroundAdelmidrol is a semisynthetic derivative of azelaic acid and analogue of the anti-inflammatory compound palmitoylethanolamide (PEA). Based upon its physicochemical properties, adelmidrol is suitable for topical application. The main objective of the present study was to evaluate the efficacy of a topical adelmidrol emulsion on early and late inflammatory responses in hypersensitive dogs. Repeated intradermal injections of Ascaris suum extract were performed in both lateral thoracic areas of six conscious hypersensitive Beagle dogs, topically treated during 8 consecutive days. Adelmidrol (2%) was applied to one side and vehicle to the other. 24 hours after the last antigen challenge, two biopsies (adelmidrol- and vehicle-treated side) were obtained for each dog at the antigen injection site.ResultsA significant reduction in the antigen-induced wheal areas was observed on the 4th and 7th day of adelmidrol treatment. Moreover, cutaneous mast cell numbers were significantly decreased in biopsies obtained after 8 consecutive days of topical adelmidrol treatment.ConclusionsThe results obtained in the present study show that topical treatment with adelmidrol might represent a new therapeutic tool in controlling the early and late allergic inflammatory skin responses in companion animals.

The anti‐inflammatory mediator palmitoylethanolamide enhances the levels of 2‐arachidonoyl‐glycerol and potentiates its actions at TRPV1 cation channels

“…Adelmidrol, a synthetic analogue of PEA with anti‐inflammatory actions in dogs (Cerrato et al ., ), had no effect on 2‐AG‐induced activation or desensitization of the TRPV1‐mediated elevation of intracellular Ca 2+ in the range of concentrations of 1 to 50 μM (Table ). Adelmidrol alone produced no stimulatory or inhibitory effect on TRPV1 channels (data not shown).…”

“…The present observation that PEA potentiation of 2‐AG desensitization of TRPV1 channels is reduced, but still present, if the two compounds are given to cells together, argues in favour of an allosteric mechanism of action. We have also tested here the effect of adelmidrol, a synthetic analogue of PEA with anti‐inflammatory actions in dogs (Cerrato et al ., ). Our results show that adelmidrol, in the range of concentrations from 1 to 50 μM, pre‐incubated 5 min before 2‐AG, had no effect on 2‐AG‐induced activation or desensitization of the TRPV1‐mediated elevation of intracellular Ca 2+ .…”

Impact of Nutritional Supplementation on Canine Dermatological Disorders

“…A single oral treatment of PEA at three different dosages (3, 10, 30 mg/kg body weight) was able to reduce, significantly and rapidly, the clinical manifestation of hypersensitivity principally at a dose of 10 mg/kg. The same study also provided additional insight concerning the pharmacokinetics of PEA, which is quickly absorbed in the stomach and reaches its maximum plasmatic concentration between the first and second hour, decreasing to the basal level within 4 h [29]. In another randomized, double-blinded vs. placebo study on canine atopic dermatitis (AD), the oral administration of 15 mg/kg/day of PEA was responsible for a statistically significant reduction in Canine Atopic Dermatitis Extent and Severity Index (CADES)-04 scores [30].…”

Review: Innate immunity, lipid metabolism and nutrition in canine atopic dermatitis

“…Systemically administered PEA has been demonstrated to decrease the wheal response after intradermal injection of antigen in dogs experimentally sensitized to A. suum . Palmitoylethanolamide (or its analogue adelmidrol) was also demonstrated to decrease the release of mast cell inflammatory mediators following anti‐IgE challenge in ex vivo skin samples . These findings led investigators to speculate that the increased levels of cutaneous fatty acids may represent an adaptive response and an attempt to downregulate cutaneous inflammation in canine AD skin .…”

“…Dogs with AD were demonstrated to have stronger immunohistochemical staining for cannabinoid receptors in their dermis compared with healthy dogs . Treatment with topical cannabinoid receptor agonists, such as palmitoylethanolamide (PEA; palmidrol) or its analogue adelmidrol, reduces canine mast cell degranulation and histamine‐induced itch and vasodilatation . Additionally, cutaneous levels of endogenous PEA have been demonstrated to be increased in the skin of atopic dogs, possibly as an attempt to downregulate cutaneous inflammation …”