Ultramicronized palmitoylethanolamide counteracts the effects of compound 48/80 in a canine skin organ culture model

Background - Ultramicronized palmitoylethanolamide (PEA-um) has been reported to reduce pruritus and skin lesions in dogs with moderate atopic dermatitis and pruritus. Hypothesis/Objectives - A canine ex vivo skin model was used to investigate the ability of PEA-um to counteract changes induced by compound 48/80, a well-known secretagogue that causes mast cell degranulation. Animals - Normal skin was obtained from three donor dogs subjected to surgery for reasons unrelated to the study. Methods - Cultured skin biopsy samples in triplicate were treated with 10 and 100 lg/mL compound 48/80, without or with 30 mu M PEA-um. Mast cell (MC) degranulation, histamine release into the culture medium, local microvascular dilatation, epidermal thickness, keratinocyte proliferation and epidermal differentiation markers were evaluated. Results - Exposure of the skin organ culture to PEA-um 24 h before and 72 h concomitantly to compound 48/80 resulted in a significant decrease of degranulating MCs. PEA-um also reduced the histamine content in the culture medium by half, although the effect did not reach statistical significance. PEA-um significantly counteracted vasodilation induced by 100 lg/mL compound 48/80. Finally, PEA-um alone did not induce changes in epidermal thickness, differentiation markers, keratinocyte proliferation, MC density and/or degranulation. Conclusions and clinical importance - Collectively, these results support the protective action PEA-um on the skin of dogs undergoing allergic changes.