title: Aromatic trap analysis of free radicals production in experimental collagen-induced arthritis in the rat: protective effect of glycosaminoglycans treatment.
abstract: Many findings demonstrated that Glycosaminoglycans (GAGs) and Proteoglycans (PGs) possess antioxidant activity. Collagen-induced arthritis (CIA) is an experimental animal model similar to human rheumatoid arthritis (RA) in which free radicals are involved. Sodium salicylate can be used as a chemical trap for hydroxyl radicals (OH*), the most damaging reactive oxygen species (ROS), yielding 2,5-dihydroxybenzoic acid), (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA). The measurement of these two acids in the plasma allows to indirectly assess the production of OH* radicals. The aim of the study was to investigate the effect of hyaluronic acid (HYA) (30 mg/kg i.p.) or chondroitin-4-sulphate (C4S) (30 mg/kg i.p.), on free radical production in Lewis rats subjected to CIA. After the immunization with bovine collagen type II in complete Freund's adjuvant, rats developed an erosive hind paw arthritis, that produced high plasma OH* levels assayed as 2,3-DHBA and 2,5-DHBA, primed lipid peroxidation, evaluated by analyzing conjugated dienes (CD) in the articular cartilage; decreased the concentration of endogenous vitamin E (VE) and catalase (CA) in the joint cartilage; enhanced macrophage inflammatory protein-2 (MIP-2) serum levels and increased elastase (ELA) evaluated as an index of activated leukocyte polymophonuclear (PMNs) accumulation in the articular joints. The administration of HYA and C4S starting at the onset of arthritis (day 11) for 20 days, limited inflammation and the clinical signs in the knee and paw, reduced OH* production, decreased CD levels, partially restored the endogenous antioxidants VE and CA, reduced MIP-2 serum levels and limited PMNs infiltration. The results indicate that the GAGs HYA and C4S significantly reduce free radical production in CIA and could be used as a tool to investigate the role of antioxidants in RA.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, School of Med., University of Messina, Policlinico Universitario, Torre Biologica, 5o piano, I-98125-Messina, Italy. gcampo@unime.it
authors.forename: Giuseppe M
authors.initials: GM
authors.lastname: Campo
authors.forename: Angela
authors.initials: A
authors.lastname: Avenoso
authors.forename: Salvatore
authors.initials: S
authors.lastname: Campo
authors.forename: Alida
authors.initials: A
authors.lastname: Ferlazzo
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Carmelo
authors.initials: C
authors.lastname: Micali
authors.forename: Alberto
authors.initials: A
authors.lastname: Calatroni
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced*; D001169:Arthritis, Experimental; D001835:Body Weight / Q000187:drug effects; D002356:Cartilage / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology*; D005609:Free Radicals; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007596:Joints / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D015846:Monokines / Q000097:blood; D009504:Neutrophils / Q000378:metabolism; D010196:Pancreatic Elastase / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000975:Antioxidants; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D005609:Free Radicals; D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D015846:Monokines; D014810:Vitamin E; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D003094:Collagen; D002374:Catalase; D010196:Pancreatic Elastase