Efficacy of treatment with glycosaminoglycans on experimental collagen-induced arthritis in rats |
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Authors: | Email author" target="_blank">Giuseppe?M?CampoEmail author Angela?Avenoso Salvatore?Campo Alida?M?Ferlazzo Domenica?Altavilla Alberto?Calatroni |
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Institution: | (1) Department of Biochemical, Physiological and Nutritional Sciences, School of Medicine, University of Messina, Messina, Italy;(2) Department of Morphology, Biochemistry, Physiology and Animal Production, School of Veterinary Medicine, University of Messina, Messina, Italy;(3) Department of Experimental and Clinical Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy |
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Abstract: | To 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. |
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