Efficacy of treatment with glycosaminoglycans on experimental collagen-induced arthritis in rats

Abstract

CIA = collagen-induced arthritis; C4S = chondroitin-4-sulphate; GAG = glycosaminoglycan; GSH = reduced glutathione; HYA = hyaluronic acid; RA = rheumatoid arthritis; ROS = reactive oxygen species; SOD = superoxide dismutase; TNF-α = tumour necrosis factor-α. (Print ISSN 1478-6354; Online ISSN 1478-6362). This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Arthritis Research & TherapyVol 5 No 3 Campo et al. Research article Efficacy of treatment with glycosaminoglycans on experimental collagen-induced arthritis in rats AbstractTo evaluate the antioxidant activity of the glycosaminoglycans hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S), we used a rat model of collagen-induced arthritis (CIA). Arthritis was induced in Lewis rats by multiple intradermal injections of 250 µl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail and into three to five other sites on the back. Rats were challenged again with the same antigen preparation 7 days later. Disease developed about 11 days after the second immunization. The effects of treatment in the rats were monitored by biochemical parameters and by macroscopic and histological evaluations in blood, synovial tissue and articular cartilage. Arthritis produced the following symptoms: severe periarticular erythema, edema and inflammation in the hindpaws; membrane peroxidation in the cartilage of the joints; endogenous antioxidant wasting; high tumour necrosis factor-α (TNF-α) plasma levels; and synovial neutrophil accumulation. Treatment with HYA and C4S, starting at the onset of arthritis for 10 days, limited the erosive action of the disease in the articular joints of knee and paw, reduced lipid peroxidation, restored the endogenous antioxidants reduced glutathione (GSH) and superoxide dismutase, decreased plasma TNF-α levels, and limited synovial neutrophil infiltration. These data confirm that erosive destruction of the joint cartilage in CIA is due at least in part to free radicals released by activated neutrophils and produced by other biochemical pathways. The beneficial effects obtained with the treatment suggest that HYA and C4S could be considered natural endogenous macromolecules to limit erosive damage in CIA or as a useful tool with which to study the involvement of free radicals in rheumatoid arthritis.

Chondroitin Sulphate: Antioxidant Properties and Beneficial Effects

“…A secondary activity of chondroitin sulphate could be an anti-inflammatory effect exerted by chelating transition metals or by scavenging ROS. The inhibition of lipid peroxidation may decrease the formation of the chemotactic intermediates thus reducing PMNs recruitment [19,20,22]. While the neutralisation of the reactive oxygen species released by activated PMNs may directly reduce inflammation.…”

“…Campo et al [19] evaluated the antioxidant activity of HA and C4S in a rat model of CIA. Treatment with the two compounds, starting at the onset of arthritis for 10 days, limited the erosive action of the disease in the articular joints of knee and paw, reduced lipid peroxidation, restored the endogenous antioxidants GSH and SOD, decreased plasma tumour necrosis factor-(TNF-) levels and limited synovial neutrophil infiltration, suggesting that erosive destruction of the joint cartilage in CIA is due at least in part to free radicals released by activated neutrophils and produced by other biochemical pathways and that hyaluronan and chondroitin-4-sulphate could be considered natural endogenous macromolecules to limit erosive damage in CIA.…”

“…Glycosaminoglycans (GAGs) have recently been suggested to show antioxidant properties mainly for hyaluronan (HA) and chondroitin-4-sulphate (C4S), in both in vitro and in vivo experimental models [17][18][19][20][21]. This antioxidant activity is probably due to their capacity to chelate transition metals like Cu ++ or Fe ++ that are in turn responsible for the initiation of Haber-Weiss and Fenton's reaction [18,21,22].…”

Effect of chondroitin sulfate on the type I collagen metabolism in the compact bone in alloxan-induced rats

“…Для вы-яснения влияния экзогенных гликозамино-гликанов на обмен костного коллагена при СД 16 животным на фоне аллоксанового диабета вводили внутримышечно хондрои-тина сульфат («Хондрогард®», ФармФирма «Сотекс»), растворённый в 0,9% растворе нат-рия хлорида в дозе 1 мг/кг массы тела [8] через день. В другой группе (n=21) хондрои-тина сульфат не применяли.…”

Quantitative analysis of chondroitin sulfate in raw materials, ophthalmic solutions, soft capsules and liquid preparations

“…It has been used clinically for the treatment of chronic diseases such as degenerative arthritis, cirrhosis, and chronic photo damage [ [5][6][7]. Although the intestinal absorption of CS is controversial due to its high molecular weight (MW) and charge density [8,9], several investigations have demonstrated the efficacy and bioavailability of CS in animals [6,[10][11][12] and humans [13][14][15][16][17]. Hence, the number of pharmaceuticals containing CS has increased as the types of formulations, which include tablets, hard capsules, soft capsules, ophthalmic solutions, and liquid preparations.…”