Xanthine oxidase and tumor necrosis pastor alpha: Possible mediators of remote tissue injury alter viper envenomation

Background: Tumor necrosis factor is associated with various local and syst emic inflammatory sequelae following snakebite. Xanthine oxidase is a princ ipal mediator of remote tissue injury (e.g., lungs, heart, liver). Objective: To investigate in a snakebite-like animal model the as yet unexp lored role of TNF and XO in mediating organ damage following snakebite. Methods: Sprague-Dawley rats were injected intra-muscularly with a non-leth al 500 mug/kg dose of Vipera aspis venom (n=10) or saline (n=10). Blood pre ssure 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 he art rate and invasive arterial pressure. The blood circulating TNF levels w ere significantly higher in the intoxicated group (P<0.05 vs. saline group) , with changes seen at 30 minutes from intoxication in both groups. Total X O + 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 activ ity in the heart was similar. Conclusions: The mediation of remote organ and hemodynamic changes followin g 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 bett er understand the role of either compound and the time frame of their activ ity before specific antagonists can be introduced for snakebite management.