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

Vet Dermatol. 2017 Oct;28(5):456-e104. doi: 10.1111/vde.12456. Epub 2017 Jun 5.

Abstract

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 μg/mL compound 48/80, without or with 30 μM 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 μg/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.

MeSH terms

  • Amides
  • Animals
  • Cell Degranulation / drug effects
  • Cell Proliferation / drug effects
  • Dogs
  • Ethanolamines / pharmacology*
  • Female
  • Histamine / metabolism
  • Keratinocytes / drug effects
  • Mast Cells / drug effects
  • Mast Cells / physiology
  • Organ Culture Techniques / methods
  • Palmitic Acids / pharmacology*
  • Skin / drug effects*
  • p-Methoxy-N-methylphenethylamine / antagonists & inhibitors*
  • p-Methoxy-N-methylphenethylamine / pharmacology

Substances

  • Amides
  • Ethanolamines
  • Palmitic Acids
  • p-Methoxy-N-methylphenethylamine
  • palmidrol
  • Histamine