title: Allopurinol inhibits CXC chemokine expression and leukocyte adhesion in endotoxemic liver injury.
abstract: OBJECTIVE
  Leukocyte activation and recruitment are rate limiting steps in endotoxemic liver injury. We investigated the effect of allopurinol on the expression of CXC chemokines and leukocyte-endothelium interactions, microvascular perfusion failure, and cellular injury and apoptosis in endotoxemic liver injury.
  
  
  METHODS
  Mice were treated with allopurinol prior to challenge with lipopolysaccharide (LPS) + D-Galactosamine (Gal). Intravital microscopy of the liver microcirculation and analysis of liver enzymes were conducted 6 h later.
  
  
  RESULTS
  We observed that allopurinol pre-treatment reduced the number of firmly adherent leukocytes by more than 57% in postsinusoidal venules of endotoxemic mice. Indeed, endotoxin-induced liver injury enzymes were decreased by 76% and sinusoidal perfusion failure was reversed in mice pre-treated with allopurinol. Moreover, administration of allopurinol reduced LPS-induced hepatocyte apoptosis by 56%. Notably, it was found that allopurinol significantly decreased the levels of CXC chemokines (more than 83% reduction) in livers of endotoxemic mice.
  
  
  CONCLUSIONS
  This study shows that allopurinol markedly protects against endotoxemic liver injury and indicates that reactive oxygen species (ROS) mediate synthesis of CXC chemokines and leukocyte adhesion in the liver in vivo.
mesh_terms: D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion / Q000187:drug effects; D019743:Chemokines, CXC / Q000096:biosynthesis*; D019446:Endotoxemia / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion; D017382:Reactive Oxygen Species
chemical_list: D019743:Chemokines, CXC; D017382:Reactive Oxygen Species; D000493:Allopurinol