MODULATION OF UVB INDUCED INFLAMMATORY SKIN DAMAGE AND REDUCTION IN MICE TUMOR INCIDENCE BY NAPROXEN TOPICAL APPLICATION.

DANIEL H. GONZÁLEZ MAGLIO; MARIELA L. PAZ; ALEJANDRO FERRARI; JORGE NIETO; JULIANA LEONI

Buenos Aires, Argentina

Congreso; 21st World Congress of Dermatology; 2007

ObjectivesTo examine the effect of the topical application of a non steroid anti-inflammatory drug (naproxen) on the epidermal damage after an acute dose of UVB radiation in hairless mice.To evaluate the effect of the topical application of the same drug on the epidermal damage and tumor development after a chronic UVB irradiation schedule in hairless mice.Materials and MethodsSKH-1 hairless mice were divided into 3 groups (3 animals each) according to the treatment: G1, non irradiated control; G2, irradiated; G3, irradiated plus naproxen (0 hours post UVB). Mice were irradiated with an acute dose of 200 mJ/cm2 and sacrificed 24 hours later; dorsal skin was removed and treated to scrape the epidermis in order to make homogenates.Other two mice groups (15 animals each) were used for chronic irradiation: G4, non irradiated control; G5, irradiated with 50 mJ/cm2, three times a week, during 4 months. Once a month 3 animals per group were challenged with an acute UVB dose (200 mJ/cm2), sacrificed and their dorsal skin treated like previously described. Pro-inflammatory molecules like PGE2 and TNF-a levels were assessed by ELISA and inducible Nitric Oxide Synthase (iNOS) expression was studied by western blot, in each epidermal homogenate sample of both acute and chronic treatments.The effect of the topical application of naproxen on tumor development was studied by assessing the number of lesions, in another chronic UVB irradiation schedule consisting of 3 groups (5 animals each): G6, irradiated; G7, irradiated plus naproxen; G8, non irradiated control (drug topical application was performed immediately after each irradiation).  ResultsAcute UVB irradiation caused a significant increase in all inflammatory mediators analyzed: PGE2 314 %, iNOS 311 % and TNF-a 203 % (G2/G1). Naproxen reduced the levels of PGE2 (6 %) and iNOS (179 %), but increased TNF-a (578 %) (G3/G1).UVB chronic irradiation caused a decrease in the response to the acute challenge; PGE2 and TNF-a levels were among 35-70% and 45-73% respectively; whereas iNOS expression only started to decrease on the 3rd and 4th month (86 % and 69 % respectively) (G5/G4).Naproxen clearly decreased the number of lesions in chronic irradiated mice, the average number of tumors developed by mice in G6 were much higher (8.67±1.53) than in G7 (2.67±2.08). G8 did not develop any tumor at all.ConclusionsTopical application of naproxen reduces short and long term UVB skin damage, since it immediately decreases the levels of inflammatory-related molecules like PGE2 and iNOS and increases TNF-a which, although it is related to inflammation, may be involved in tumoral cells elimination, as seen in the reduction of mice tumor incidence.