Protection from Oxygen Toxicity with Endotoxin

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Abstract
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.