Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties

J Cosmet Dermatol. 2017 Dec;16(4):e59-e67. doi: 10.1111/jocd.12349. Epub 2017 Jun 7.

Abstract

Background: Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response.

Aims: In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g).

Methods: We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response.

Results: Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property.

Conclusion: In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients.

Keywords: anti-inflammatory; antihistamines; dexchlorpheniramine; phototoxicity; promethazine; skin barrier.

Publication types

  • Comparative Study

MeSH terms

  • 3T3 Cells
  • Animals
  • Chlorpheniramine / adverse effects
  • Chlorpheniramine / pharmacology*
  • Dermatitis, Phototoxic / etiology
  • Dermatitis, Phototoxic / metabolism*
  • Dermatitis, Phototoxic / prevention & control
  • Dinoprostone / metabolism
  • Female
  • Histamine / metabolism
  • Histamine H1 Antagonists / adverse effects
  • Histamine H1 Antagonists / pharmacology*
  • Humans
  • Interleukin-1 / metabolism
  • Keratin-14 / metabolism
  • Leukotriene B4 / metabolism
  • Mice
  • Middle Aged
  • NF-kappa B / metabolism
  • Promethazine / adverse effects
  • Promethazine / pharmacology*
  • Protein Precursors / metabolism
  • Skin / metabolism
  • Skin Cream / adverse effects
  • Skin Physiological Phenomena / drug effects
  • TRPV Cation Channels / metabolism
  • Tissue Culture Techniques
  • Ultraviolet Rays / adverse effects
  • beta-Endorphin / metabolism

Substances

  • Histamine H1 Antagonists
  • Interleukin-1
  • Keratin-14
  • NF-kappa B
  • Protein Precursors
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Leukotriene B4
  • dexchlorpheniramine
  • Chlorpheniramine
  • involucrin
  • beta-Endorphin
  • Histamine
  • Promethazine
  • Dinoprostone