Potentiation of paraquat lethality in mice by bacterial lipopolysaccharide pretreatment

Mice treated with Escherichia coli endotoxin (500 micrograms/kg i.p.) 24 and 1 hr before paraquat dichloride (50 mg/kg i.p.) had a 2-fold increase in 7-day cumulative mortality compared to those injected with buffered saline before paraquat. The duration of the prior exposure time to endotoxin appears to be an important determinant of the potentiating effect as more mice died after 24 than 1 hr pretreatment. The potentiating effect of endotoxin on paraquat-induced lethality is not due to increased uptake of the toxicant. Lung values of radioactivity from [14C]paraquat were not significantly different between endotoxin and buffered saline-treated mice. Despite the potentiating effect of endotoxin on paraquat-induced lethality, it appears that the lipopolysaccharide is able to provide some protection to the pulmonary capillary endothelium because pretreatment reverses an increase in serum angiotensin converting enzyme. Although not addressed in the present investigation, possible mechanisms for the potentiating effect of endotoxin on paraquat-induced lethality may involve superoxide anion generation, superoxide dismutase inhibition or both.