Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis.
Glucosamine sulfate (GS) is a glycosaminoglycan with anti-inflammatory and immunoregulatory properties. Here we set out to explore the effect of GS administration on markers of systemic and local inflammation in rabbits with atherosclerosis aggravated by chronic arthritis. Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intra-articular injections of ovalbumin in previously immunized rabbits. A group of these rabbits was treated prophylactically with oral GS (500 mg.kg(-1).day(-1)), and, when the animals were killed, serum was extracted and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, the femoral arteries, thoracic aorta, and synovial membranes were examined in gene expression studies and histologically. GS administration reduced circulating levels of the C-reactive protein and of interleukin-6. GS also lowered nuclear factor-kappaB activation in PBMC, and it downregulated the expression of both the CCL2 (monocyte chemoattractant protein) and cyclooxygenase-2 genes in these cells. Lesions at the femoral wall were milder after GS treatment, as reflected by the intimal-to-media thickened ratio and the absence of aortic lesions. Indeed, GS also attenuated the histological lesions in synovial tissue. In a combined rabbit model of chronic arthritis and atherosclerosis, orally administered GS reduced the markers of inflammation in peripheral blood, as well as the femoral and synovial membrane lesions. GS also prevented the development of inflammation-associated aortic lesions. These results suggest an atheroprotective effect of GS.
Largo
Raquel
R
Joint and Bone Research Laboratory, Fundación Jimenez Diaz, Reyes Católicos 2, Universidad Autónoma, Madrid, Spain. rlargo@fjd.es
Martínez-Calatrava
María José
MJ
Sánchez-Pernaute
Olga
O
Marcos
M Esther
ME
Moreno-Rubio
Juan
J
Aparicio
César
C
Egido
Jesús
J
Herrero-Beaumont
Gabriel
G
D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000473:pathology*; D050197:Atherosclerosis / Q000150:complications / Q000473:pathology*; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005263:Femoral Artery / Q000473:pathology; D005944:Glucosamine / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000473:pathology
D018932:Chemokine CCL2; D015850:Interleukin-6; D008055:Lipids; D016328:NF-kappa B; D012313:RNA; D010047:Ovalbumin; D002097:C-Reactive Protein; D051546:Cyclooxygenase 2; D005944:Glucosamine