Boyd M R, Catignani G L, Sasame H A, Mitchell J R, Stiko A W
Am Rev Respir Dis. 1979 Jul;120(1):93-9. doi: 10.1164/arrd.1979.120.1.93.
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.
给大鼠皮下注射呋喃妥因会导致严重的肺部损伤，其特征为水肿、充血和出血。与喂食美国国立卫生研究院开放式配方饮食的大鼠相比，喂食高多不饱和脂肪的维生素E缺乏饮食的大鼠中该药物的急性致死率更高。如果在给呋喃妥因前3周给缺乏维生素E的大鼠喂食补充了维生素E的饮食和/或含有饱和脂肪（猪油）的饮食，这些动物的存活时间会延长。在缺乏维生素E的大鼠以及补充了维生素E并暴露于富氧环境的大鼠中，呋喃妥因的毒性均增强。这些结果，结合之前在体外进行的代谢研究表明在呋喃妥因存在的情况下大鼠肺微粒体中有氧化还原循环和氧气活化，说明了与肺毒性除草剂百草枯有某些相似之处，并提出了这两种药物是否可能通过共同机制损害肺部的问题。
