title: Xanthine oxidase and tumor necrosis factor alpha: possible mediators of remote tissue injury after viper envenomation.
abstract: BACKGROUND
  Tumor necrosis factor is associated with various local and systemic inflammatory sequelae following snakebite. Xanthine oxidase is a principal mediator of remote tissue injury (e.g., lungs, heart, liver).
  
  
  OBJECTIVE
  To investigate in a snakebite-like animal model the as yet unexplored role of TNF and XO in mediating organ damage following snakebite.
  
  
  METHODS
  Sprague-Dawley rats were injected intramuscularly with a non-lethal 500 micrograms/kg dose of Vipera aspis venom (n = 10) or saline (n = 10). Blood pressure and heart rate were continuously monitored, TNF-alpha was measured in the blood, and total XO + xanthine dehydrogenase activity was assessed in various tissues. Lung histology and permeability indices were analyzed.
  
  
  RESULTS
  Venom injection caused a significant (P < 0.05) reduction in both heart rate and invasive arterial pressure. The blood circulating TNF levels were significantly higher in the intoxicated group (P < 0.05 vs. saline group), with changes seen at 30 minutes from intoxication in both groups. Total XO + XDH activity in the kidney, lung and liver of the venom-injected group was significantly (P < 0.05) higher than in the saline group, while the activity in the heart was similar.
  
  
  CONCLUSIONS
  The mediation of remote organ and hemodynamic changes following intramuscular injection of a non-lethal dose of Vipera aspis venom can be attributed partly to TNF and partly to XO. More research is needed to better understand the role of either compound and the time frame of their activity before specific antagonists can be introduced for snakebite management.
authors.affiliation: General Intensive Care Unit, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Szold
authors.forename: A A
authors.initials: AA
authors.lastname: Weinbroum
authors.forename: R
authors.initials: R
authors.lastname: Ben-Abraham
authors.forename: T E
authors.initials: TE
authors.lastname: Englender
authors.forename: D
authors.initials: D
authors.lastname: Ovadia
authors.forename: P
authors.initials: P
authors.lastname: Sorkine
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D012909:Snake Bites / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014688:Venoms; D017819:Viperidae; D014969:Xanthine Oxidase / Q000097:blood*
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D014688:Venoms; D014969:Xanthine Oxidase