Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oxygen.

The subcutaneous administration of nitrofurantoin to rats caused severe pulmonary damage, characterized by edema, congestion, and hemorrhage. The acute lethality of the drug was greater in rats fed vitamin E-deficient diets high in polyunsaturated fats as compared to rats fed the NIH open-formula diet. The survival times of vitamin E-deficient rats were increased if such animals were fed diets supplemented with vitamin E and/or diets containing saturated fat (lard) for 3 weeks before administration of nitrofurantoin. The toxicity of nitrofurantoin was enhanced in both the rats deficient in vitamin E and in those given vitamin E supplements and exposed to O2-enriched atmospheres. These results, in conjunction with previous metabolic studies in vitro showing redox cycling and O2 activation in rat lung microsomes in the presence of nitrofurantoin, illustrate certain similarities with the lung-toxic herbicide, paraquat, and raise the question of whether the 2 agents may be capable of damaging lungs by a common mechanism.