Effect of scavengers of oxygen-derived free radicals on mortality in endotoxin-challenged mice

Oxygen-derived free radicals have been implicated as mediators of cellular injury in several model systems. Recently, a role for free radicals has been proposed in the mortality associated with Gram-negative bacterial sepsis. To determine if pretreatment with free radical scavengers can prevent endotoxin-induced mortality, mice rendered sensitive to endotoxin with actinomycin D were treated with either superoxide dismutase (SOD), N-acetylcysteine (NAC) or saline and were then challenged with a dose of endotoxin calculated to cause a mortality of greater than 80%. Mortality was assessed at 12-h intervals after challenge. Increased survival was seen in the SOD-treated group compared to the control group (p less than or equal to .05). In contrast, survival in mice treated with NAC, another potential scavenger, was not significantly different from the control group. These results support the hypothesis that superoxide and hydroxyl radicals contribute to mortality in Gram-negative bacterial sepsis.