INVESTIGADORES
GONZALEZ MAGLIO Daniel Horacio
congresos y reuniones científicas
Título:
EFFECT OF GLUCOSAMINE AND MELOXICAM ORAL ADMINISTRATION ON AN ACUTE ARTICULAR INFLAMMATORY MODEL
Autor/es:
PAZ, MARIELA L; GONZALEZ MAGLIO, DANIEL H; WEILL, FEDERICO; FERRARI, ALEJANDRO; CELA, ELIANA M; NIETO, JORGE D.; LEONI, JULIANA
Lugar:
Copenague
Reunión:
Congreso; EULAR 2009; 2009
Resumen:
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EFFECT OF GLUCOSAMINE AND
MELOXICAM ORAL ADMINISTRATION ON AN ACUTE ARTICULAR INFLAMMATORY MODEL
M. L. Paz*1,
D. H. González Maglio1, F. S. Weill1, A. Ferrari1,
E. M. Cela1, J. D. Nieto2, J. Leoni11Immunology, Pharmacy and
Biochemistry School - UBA, 2R+D, Asofarma S.A., C.A.B.A., Argentina
Background: Several studies have
shown that individuals affected by osteoarticular diseases have a cartilage
matrix with an exacerbated renewal rate and inadequate repair mechanisms1.
For that reason, it has been stated that oral administration of a NSAID, like
Meloxicam (Mxc), could relieve the symptoms of arthritis, like inflammation,
swelling, stiffness and articular pain2, and that the
administration of a matrix precursor, like glucosamine (GlcN), may enhance
matrix reconstitution3. Also, some reports performed with cultured
human chondrocytes indicated that GlcN could have a direct effect on the
inflammatory mediators4. However, there are yet no reports
concerning the biochemical effect of in vivo oral administration of GlcN and a
NSAID. Objectives: The aim of the present
study was to analyze the effect of the oral administration of GlcN, Mxc and a
mixed formulation (GlcN-Mxc), on an animal model of articular inflammation. The
project was divided in two phases; a) evaluation of inflammatory mediators
profile following articular injury; b) evaluation of the effects of oral
administration of GlcN, Mxc and GlcN-Mxc. Methods: The animal model
consisted of Wistar rats of 200 grs. All animals were treated according to the
international standards, and handling was performed under light anaesthesia.
The evaluation of the cytokine profile was performed using 6 groups of animals
with 5 animals each. All animals, except a control group (CG), received the
inflammatory stimulus (IS), which consisted of two intraarticular
administrations of complete Freund Adjuvant. Animals were sacrificed at 12, 24,
48, 72 and 96 hs after the IS, and mediators were measured in both rear
articulations. The animal model was then set up to test the effect of GlcN and
Mxc; IL-1eta, PGE2 and iNOS expression were measured, as well as
gastric integrity after oral treatment. Results: The results indicate
that both PGE2 and IL-1eta were increased during the first 24 to 30
hs after articular injury, and therefore all further measurements were
performed 24 hs after the last IS. Oral administration of Mxc and GlcN-Mxc led
to an equivalent decrease of PGE2, when compared to the placebo
group (p<0.001). GlcN-Mxc produced a more pronounced decrease in iNOS
expression (p<0.001) than Mxc (p<0.01), reinforcing the benefits of this
combination. IL-1eta levels remained unaltered following oral treatments, and
none of these produced gastric damage.
Conclusion: Oral
administration of GlcN-Mxc efficiently decreases the intraarticular levels of
inflammatory-related molecules like PGE2 and iNOS, and this effect
is less intense when drugs are tested alone. Therefore, this study supports the
suitability of an oral treatment with a combination of these drugs. References: 1.
Dieppe P. "Osteoarthritis and molecular markers: a rheumatologist´s
prospective". Acta Orthop. Scand. 66, 1995, Suppl. 266: I.
2. Jones CJ, et al. "In vivo effects of meloxicam and aspirin on blood,
gastric mucosal, and synovial fluid prostanoid synthesis in dogs". Am. J.
Vet. Res., 2002, 63: 1527-31.
3. Deal, CL. Neutraceuticals as Therapeutic Agents in Osteoarthritis.
Rheumatic Disease Clinics of North America. 1999: 379-395.
4. Alexander R, et al. "N-Acetylglucosamine Prevents IL-1eta mediated
activation of Human Chondrocytes". J. Immunol. 2001, 166: 5155-60.