title: Chondroitin-4-sulphate reduced oxidative injury in caerulein-induced pancreatitis in mice: the involvement of NF-kappaB translocation and apoptosis activation.
abstract: Activation of nuclear factor kappaB (NF-kappaB) and caspases may greatly amplify inflammation and cell damage in addition to that directly exerted by free radicals. Since reactive oxygen species (ROS) are involved in acute pancreatitis, we studied whether the administration of chondroitin-4-sulphate (C4S), in addition to its antioxidant activity, was able to modulate NF-kappaB and caspase activation in an experimental model of caerulein-induced acute pancreatitis in mice. Hyperstimulating doses of caerulein (50 microg/ kg), five injections per mouse given at hourly intervals produced the following: high serum lipase and amylase activity; lipid peroxidation, evaluated by 8-isoprostane concentrations; loss of antioxidant defenses such as glutathione reductase (GR) activity; NF-kappaB activation and loss of cytoplasmic IkappaBalpha protein; increases in tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), caspase-3, and caspase-7 gene expression and their related protein; accumulation and activation of neutrophils in the damaged tissue, evaluated by elastase (ELA) determination; and pancreatic injury, evaluated by histologic analysis. Pretreatment of mice with different doses of C4S, given 1 hr before caerulein injections and 1 and 2 hrs after the last caerulein injection, reduced lipid peroxidation, inhibited NF-kappaB translocation and cytoplasmic IkappaBalpha protein loss, decreased TNF-alpha, IL-6, and caspase gene expression and their related protein levels, limited endogenous antioxidant depletion, and reduced tissue neutrophils accumulation and tissue damage. Since molecules with antioxidant activity can block NF-kappaB and apoptosis activation, we suggest that C4S administration is able to block NF-kappaB and caspase activation by reducing the oxidative burst.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, School of Medicine, University of Messina, Policlinico Universitario, 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: Giancarlo
authors.initials: G
authors.lastname: Nastasi
authors.forename: Paola
authors.initials: P
authors.lastname: Traina
authors.forename: Angela
authors.initials: A
authors.lastname: D'Ascola
authors.forename: Alberto
authors.initials: A
authors.lastname: Calatroni
mesh_terms: D000818:Animals; D017209:Apoptosis; D002108:Ceruletide / Q000494:pharmacology*; D002809:Chondroitin Sulfates / Q000737:chemistry*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005980:Glutathione Reductase / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D010195:Pancreatitis / Q000139:chemically induced*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide; D002809:Chondroitin Sulfates; D005980:Glutathione Reductase; D008049:Lipase