Peterson F J, Combs G F, Holtzman J L, Mason R P
J Nutr. 1982 Sep;112(9):1741-6. doi: 10.1093/jn/112.9.1741.
The acute toxicity of nitrofurantoin was studied in the young chick deficient in selenium (Se) and/or vitamin E (E). This new and potentially valuable animal model proved to be very sensitive to the toxicity of this nitro drug. The 48-hour LD50 for nitrofurantoin decreased from 148 mg/kg in the Se- and E-supplemented chicks to 53 mg/kg in Se- and E-deficient chicks. The addition of Se (0.10 ppm as Na2SeO3) alone, but not E (100 IU/kg diet as dl-alpha-tocopheryl acetate) reduced the toxicity of nitrofurantoin, so that the LD50 for the chicks given Se alone was the same as the LD50 for the E- and Se-fed chicks. Se and E deficiency significantly decreased the Se-dependent glutathione peroxidase and the plasma tocopherol levels. Hepatic glutathione content, hepatic catalase and superoxide dismutase were unchanged by the dietary treatments. However, a toxic dose of nitrofurantoin significantly decreased hepatic glutathione content over time. These data support the concept that the toxicity of this drug may be mediated in part by an oxidative stress generated by the futile reductive metabolism of the parent compound.
在缺乏硒（Se）和/或维生素E（E）的幼雏中研究了呋喃妥因的急性毒性。这种新的且具有潜在价值的动物模型被证明对这种硝基药物的毒性非常敏感。呋喃妥因的48小时半数致死剂量（LD50）从补充硒和维生素E的雏鸡的148毫克/千克降至缺乏硒和维生素E的雏鸡的53毫克/千克。单独添加硒（以亚硒酸钠形式添加0.10 ppm）可降低呋喃妥因的毒性，但单独添加维生素E（以dl-α-生育酚醋酸酯形式添加100 IU/千克日粮）则不能，因此仅给予硒的雏鸡的LD50与同时给予硒和维生素E的雏鸡的LD50相同。硒和维生素E缺乏显著降低了依赖硒的谷胱甘肽过氧化物酶和血浆生育酚水平。饮食处理对肝脏谷胱甘肽含量、肝脏过氧化氢酶和超氧化物歧化酶没有影响。然而，随着时间的推移，呋喃妥因的毒性剂量会显著降低肝脏谷胱甘肽含量。这些数据支持这样一种观点，即这种药物的毒性可能部分由母体化合物无效的还原代谢产生的氧化应激介导。
