title: Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock.
abstract: BACKGROUND
  Severe pathogenic infection triggers excessive release of cytokines as part of the massive inflammatory response associated with septic shock.
  
  
  OBJECTIVE
  To investigate the protective effect of caffeic acid phenethyl ester (CAPE) against lipopolysaccharide (LPS) induced endotoxemia, hepatic and neuronal damage and the associated systemic inflammatory response (SIR).
  
  
  METHODS
  Fifty male Wister rats were divided into: control, LPS, and CAPE+LPS groups. Plasma concentrations of various cytokines, including TNF-α, IL-1α, IL-1β, IL-6, IL-4, IL-10, and sICAM-1 were evaluated. In addition, the histopathological changes in the hepatic and neural cells were assessed.
  
  
  RESULTS
  The LPS group showed high inflammatory cytokines and sICAM-1 levels reflecting the presence of SIR. Hepatocyte necrosis, apoptosis, extensive hemorrhage and inflammatory cellular infiltration together with brain astrocytes swelling, early neuron injury and presence of inflammatory foci confirmed the toxic tissue damage. Use of CAPE decreased the inflammatory cytokines and increased the anti-inflammatory cytokines levels. This biochemical evidence of decreased SIR was confirmed histologically by decreased cellular infiltration in the liver and brain tissue which coincides with preserved structure and protection of the liver and brain cells from the toxic effects of LPS.
  
  
  CONCLUSIONS
  The ability of CAPE to alleviate the SIR, hepatic and neuronal cell damage induced by LPS and galactosamine could be attributed to its ability to reverse the imbalance of the pro- and anti-inflammatory cytokines which may lead to the inhibition of adhesion molecules' expression. CAPE is a promising agent that could help in the prophylaxis and treatment of septic shock.
authors.affiliation: Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia. iaidakorish@yahoo.com
authors.forename: Aida Abdelhamid
authors.initials: AA
authors.lastname: Korish
authors.forename: Maha Mohamed
authors.initials: MM
authors.lastname: Arafa
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002109:Caffeic Acids / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D005688:Galactosamine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000517:prevention & control*
chemical_list: D002109:Caffeic Acids; D016207:Cytokines; D008070:Lipopolysaccharides; D005688:Galactosamine; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol