Abstract
Oxygen-derived free radicals have been associated with many forms of cell injury and types of organ dysfunction, includino recently in a rat model of gram-negative sepsis. A possible source of free radicals in this setting is through activity of the enzyme xanthine oxidase, as has been shown in reperfusion injury. The purpose of this study was to determine the effect of pretreatment with allopuinol, a xanthine oxidase inhibitor, on mortality in a mouse model of endotoxin shock.
Methods. Sixty mice were divided into 2 equal groups. Treatment group received allopurinol, 50 mg/kg/day in 0.5 ml water by gavage feed each of 4 days prior to endotoxin challenge. Control animals received water gavage alone. Animals were challenged with 0.05 meg of intraperitoneal endotoxin (E. Coli 0111:B4) following dactinomycin sensitization according to a model previously described by this laboratory. Mice were checked every 24 hours.for survival.
Results. Mortality for the control and treated groups at 96 hours were 32% and 46% respectively. These rates were not statistically different; nor were differences in mortality between the two groups demonstrated at 24, 48 or 72 hours.
Conclusions. These data do not support an important role for free radicals generated by the xanthine oxidase system in this model, and suggest another, as yet undetermined source of radicals influencing mortality in endotoxemia.
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Stidham, G., Shenep, J. & Broner, C. LACK OF EFFECT OF ALLOPURINOL ON MORTALITY IN A MOUSE MODEL OF ENDOTOXIC SHOCK. Pediatr Res 21 (Suppl 4), 207 (1987). https://doi.org/10.1203/00006450-198704010-00245
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DOI: https://doi.org/10.1203/00006450-198704010-00245