Endotoxin treatment of adult rats before hyperoxic exposure significantly increases their survival rate in >95% O₂ (J. Clin. Invest.61: 269, 1978). In this study, we wished to determine: (a) whether endotoxin would protect against O₂ toxicity if it were administered after the animals were already in >95% O₂ for 12-48 h; and (b) the relationship between the endogenous antioxidant enzymes of the lung and the protective effect of endotoxin treatment.

Our results showed that adult rats given a single 500 μg/kg dose of endotoxin up to 36 h after the onset of O₂ exposure had significantly increased survival rates and decreased lung fluid accumulation compared to untreated animals in O₂ (P < 0.05). (Survival, 16/49 [untreated rats]; 18/20 [endotoxin at 12 h after the start of O₂ exposure]; 25/26 [endotoxin-24 h]; 15/20 [endotoxin-36 h].)

Endotoxin-treated animals in O₂ showed increases in pulmonary superoxide dismutase, catalase, and glutathione peroxidase activities before the usual time of onset of measurable pulmonary edema in untreated animals in O₂. When diethyldithiocarbamate was used to block the superoxide dismutase enzyme rise in the endotoxin-treated rats in O₂, the protective action of endotoxin against pulmonary O₂ toxicity was nullified. In endotoxin-treated, O₂-exposed mice, there were no lung antioxidant enzyme increases, and no protective effect from O₂ toxicity was achieved.

We conclude that, in the rat, a single dose of endotoxin given even 36 h after the onset of hyperoxic exposure results in marked protection against O₂-induced lung damage; and the increased lung antioxidant enzyme activity in the endotoxin-treated rats appears to be an essential component of this protective action.