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First published online April 11, 2008
Experimental Biology and Medicine doi: 10.3181/0711-RM-318
© 2008 by the Society for Experimental Biology and Medicine
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Regular Manuscript

CHONDROITIN-4-SULPHATE REDUCED OXIDATIVE INJURY IN CAERULEIN-INDUCED PANCREATITIS IN MICE: THE INVOLVEMENT OF NF-kB TRANSLOCATION AND APOPTOSIS ACTIVATION

Giuseppe Campo 1*, Angela Avenoso 2, Salvatore Campo 2, Giancarlo Nastasi 2, Paola Traina 2, Angela D'Ascola 2, and Alberto Calatroni 2

1 University of Messina, Italy
2 University of Messina

* To whom correspondence should be addressed. E-mail: gcampo{at}unime.it.


  Abstract

Activation of nuclear factor kB (NF-kB) 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 their antioxidant activity, was able to modulate NF-kB and caspase activation in an experimental model of caerulein-induced acute pancreatitis in mice. Hyper-stimulating doses of caerulein (50 microg/kg,, five injections per mouse given at hourly intervals) produced: high serum lipase and amylase activity; lipid peroxidation, evaluated by 8-isoprostane concentrations; loss of antioxidant defences such as glutathione reductase (GR) activity; NF-kB activation and loss of cytoplasmic IkB-alpha 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 histological analysis. Pre-treatment of mice with different doses C4S, given 1 h before caerulein injections and 1 and 2 h after the last caerulein injection, reduced lipid peroxidation, inhibited NF-kB translocation and cytoplasmic IkB-alpha protein loss, decreased TNF-alpha, IL-6 and caspase gene expression and their related protein levels, limited endogenous antioxidant depletion, reduced tissue neutrophils accumulation and tissue damage. Since molecules with antioxidant activity can block NF-kB and apoptosis activation, we suggest that C4S administration was able to block NF-kB and caspase activation by reducing the oxidative burst.

Key Words: acute pancreatitis, oxidative stress, glycosaminoglycans, caspases, antioxidants






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Copyright © 2008 by the Society for Experimental Biology and Medicine.