INVESTIGADORES
GONZALEZ MAGLIO Daniel Horacio
congresos y reuniones científicas
Título:
"Modulation of UVB Induced Inflammatory Skin Damage and Reduction in Mice Tumor Incidence by Naproxen Topical Application"
Autor/es:
GONZÁLEZ MAGLIO, DANIEL H.; PAZ, MARIELA L; FERRARI, ALEJANDRO; NIETO, JORGE D.; LEONI, JULIANA
Lugar:
Buenos Aires, Argentina.
Reunión:
Congreso; 21st World Congress of Dermatology; 2007
Resumen:
Objectives
·
To
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 Methods
SKH-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).
Results
Acute 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.
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-a which, although it is
related to inflammation, may be involved in tumoral cells elimination, as seen
in the reduction of mice tumor incidence.