title: Chondroitin-4-sulphate inhibits NF-kB translocation and caspase activation in collagen-induced arthritis in mice.
abstract: OBJECTIVE
  Free radical damage, inflammation, and apoptosis play a critical role in the onset and progression of cartilage erosion in arthritis. Many studies have demonstrated that glycosaminoglycans (GAGs), and chondroitin-4-sulphate (C4S) in particular, possess antioxidant activity that is able to inhibit lipid peroxidation which is the main mechanism of free radical-mediated biological injury. In addition to the effect directly exerted by reactive oxygen species (ROS), the activation of nuclear factor kB (NF-kB) and caspases may contribute substantially to increase inflammation and cell damage. We studied whether the antioxidant action of chronic C4S treatment to reduce ROS injury involves NF-kB and caspases modulation using an experimental model of collagen-induced arthritis in mice.
  
  
  METHODS
  Arthritis was induced in mice via an intradermal injection at the base of the tail of 100 microl of emulsion containing bovine type II collagen in complete Freund's adjuvant.
  
  
  RESULTS
  Arthritis provoked the following: severe oedema and inflammation in the hind paws; lipid peroxidation in the joints [measured by 8-isoprostane (8-IPE) levels]; reduction of the endogenous antioxidants catalase (CAT) activity and reduced glutathione (GSH) levels; induction of NF-kB translocation; a loss of cytoplasmic NF-kB inhibitor alpha (IkBalpha); an increase in metalloproteinase-13 (MMP-13), caspase-3 and caspase-7 gene expression and their related protein; the induction of cartilage polymorphonuclear (PMN) activation and infiltration [evaluated by elastase (ELA) assay] and cartilage alterations evaluated by histological analysis. Intraperitoneal administration of different doses of C4S (for 25 days), ameliorated all the symptoms of inflammation in the articular knee and paw joints, limited lipid peroxidation, inhibited NF-kB activation and IkBalpha protein loss, decreased mRNA MMP-13 and caspases expression and their related protein, restored endogenous antioxidants, and reduced PMN accumulation in the damaged cartilage.
  
  
  CONCLUSIONS
  The evidence that C4S was able to inhibit NF-kB and apoptosis activation supports the hypothesis that the C4S effect depends on reduction of ROS production, although other direct effects cannot be excluded.
authors.affiliation: Department of Biochemical, School of Medicine, University of Messina, Policlinico Universitario, Messina, Italy. gcampo@unime.it
authors.forename: G M
authors.initials: GM
authors.lastname: Campo
authors.forename: A
authors.initials: A
authors.lastname: Avenoso
authors.forename: S
authors.initials: S
authors.lastname: Campo
authors.forename: A
authors.initials: A
authors.lastname: D'Ascola
authors.forename: P
authors.initials: P
authors.lastname: Traina
authors.forename: A
authors.initials: A
authors.lastname: Calatroni
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000378:metabolism*; D061945:Caspase Inhibitors; D002809:Chondroitin Sulfates / Q000502:physiology*; D005609:Free Radicals / Q000378:metabolism; D007719:Knee Joint / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D000975:Antioxidants; D061945:Caspase Inhibitors; D005609:Free Radicals; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D002809:Chondroitin Sulfates