"Modulation of UVB Induced Inflammatory Skin Damage and Reduction in Mice Tumor Incidence by Naproxen Topical Application"

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

Buenos Aires

Congreso; 21st World Congress of Dermatology,; 2007

Society of Investigative Dermatology

5724 MODULATION OF UVB INDUCED INFLAMMATORY SKIN DAMAGE AND REDUCTION IN MICE TUMOR INCIDENCE BY NAPROXEN TDPICAL APPLICATION DH Gonzalez Maglio1, ML Pazl, A Ferrari1, JD Nieto2, J Leonil 1Facultad de Farmacia y Bioqulmica, Universidad de Buenos Aires, Buenos Aires, Argentina, 2Laboratorios Stein, San lose, Costa Rica.   Objectives • To examine the effect of the topical application of a non steroid anti-infIammatory 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 Methods SKH-1 hairless mice were divided into 3 groups i3 animals each) according to the treatment: G1, non irradiated control; G2, irradiated; G3, irradiated plus naproxen (0 hours post UVB). lvlice were irradiated with an acute dose of 200 mllcmi and sacrificed 24 hs 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 mlfcmi, 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 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).   Results Acute UVB irradiation caused a significant increase in all inflammatory mediators analyzed: PGE2 314%, iNOS 311% and TNF on 203% (G2/G1). Naproxen reduced the levels of PGE2 (6%) and iNOS (179%), but increased TNF (578%) (G3/G1). UVB chronic irradiation caused a decrease in the response to the acute challenge; PGE2 and TNF or levels were among 35-70% and 45-73% respectively; whereas iNOS expression only started to decrease on the 3th 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 (2-673:2.08). G8 did not develop any tumor at all.   Conclusions Topical 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 which, although it is related to inflammation, may be involved in the elimination of turnoral cells, as seen in the reduction of mice tumor incidence.