Topical cis-urocanic acid attenuates oedema and erythema in acute and subacute skin inflammation in the mouse.

Abstract

BACKGROUND:

cis-Urocanic acid (cis-UCA) is an endogenous immunosuppressive molecule of the epidermis.

OBJECTIVES:

 We investigated the effects of topical cis-UCA creams (2·5% and 5%) in acute and subacute mouse models of skin inflammation.

METHODS:

Acute skin irritation was induced by applying dimethyl sulphoxide (DMSO) on the earlobe of CD-1 mice. Topical cis-UCA, hydrocortisone (1%) or tacrolimus (0·1%) were applied 10 min later. In another model, subacute inflammation was provoked and maintained by three applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the ears of NMRI mice on days 1, 2 and 4. The test products were applied topically twice a day during 6 days.

RESULTS:

In the acute DMSO model, cis-UCA creams suppressed ear swelling at 1 h significantly more efficiently than hydrocortisone (P < 0·01) and tacrolimus (P < 0·001). Ear swelling was significantly inhibited by cis-UCA (P < 0·001) in the subacute TPA model as well. The 5% cream also decreased erythema, whereas tacrolimus enhanced skin reddening. Treatments with cis-UCA did not affect TPA-induced infiltration of neutrophils to the skin. In contrast to hydrocortisone, cis-UCA did not reduce epidermal thickness.

CONCLUSIONS:

The results suggest that cis-UCA - unlike hydrocortisone and tacrolimus - is efficient in both acute and subacute skin inflammation, attenuating skin oedema and erythema. Topical drug therapy with cis-UCA may provide a safe and effective drug treatment modality in inflammatory skin disorders.

• Authors: J K Laihia, P Taimen, H Kujari, L Leino
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 167 Issue 3 Pg. 506-13 (Sep 2012) ISSN: 1365-2133 [Electronic] England
• PMID: 22540389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Chemical References

• 12-O-tetradecanoylphorbol-1,3-acetate
• Dermatologic Agents
• Irritants
• Urocanic Acid
• Tetradecanoylphorbol Acetate
• Dimethyl Sulfoxide

Topics

• Acute Disease
• Administration, Cutaneous
• Animals
• Dermatologic Agents (administration & dosage, pharmacology)
• Dimethyl Sulfoxide (toxicity)
• Drug Eruptions (drug therapy, etiology)
• Edema (drug therapy)
• Erythema (drug therapy)
• Irritants (toxicity)
• Male
• Mice
• Neutrophil Infiltration (drug effects)
• Tetradecanoylphorbol Acetate (analogs & derivatives, toxicity)
• Urocanic Acid (administration & dosage, pharmacology)