Effect of Glucosamine and Meloxicam Oral Administration on an Acute Articular Inflammatory Model

MARIELA L. PAZ; DANIEL H. GONZÁLEZ MAGLIO; FEDERICO S. WEILL; ALEJANDRO FERRARI; ELIANA CELA; JORGE NIETO; JULIANA LEONI

Copenhagen, Denmark

Congreso; The European League Against Rheumatism (EULAR) Annual Meeting; 2009

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 pain”2, 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.