Lim L O, Bortell R, Neims A H
Toxicol Appl Pharmacol. 1986 Jul;84(3):493-9. doi: 10.1016/0041-008x(86)90254-1.
In our study, nitrofurantoin (NF) and nitrofurazone (NZ) inhibited respiration of isolated mouse (C57B/6J, adult, male) liver mitochondria. Other aromatic nitro compounds, nitroimidazole, metronidazole, and p-nitrobenzoic acid, did not have any significant effect. The primary site of activity for NF was complex I NADH-ubiquinone oxidoreductase mediated respiration, since only complex I substrates, glutamate, beta-hydroxybutyrate, and alpha-ketoglutarate-mediated respiration were decreased. Respiration supported by succinate, a complex II substrate, was not affected by any of the compounds. NF at a concentration of 50 microM decreased state 3 and dinitrophenol-uncoupled respiration to 28 +/- 1 and 25 +/- 5% of control, respectively, of mitochondria oxidizing glutamate. Studies with mitoplasts oxidizing glutamate showed that NF inhibited both state 3 and 4 respiration. The inhibition of state 3 was prevented by the simultaneous addition of superoxide dismutase (240 micrograms/ml) and catalase (200 micrograms/ml). These results suggest that the mitochondrion, in particular complex I of the electron transport system, is a target for NF toxicity. The effect on respiration may be mediated by NF redox cycling and the generation of reactive oxygen intermediates resulting in the interference of electron flow.
在我们的研究中，呋喃妥因（NF）和呋喃西林（NZ）抑制了分离的小鼠（C57B/6J，成年雄性）肝脏线粒体的呼吸作用。其他芳香族硝基化合物、硝基咪唑、甲硝唑和对硝基苯甲酸没有任何显著影响。NF的主要作用位点是复合体I烟酰胺腺嘌呤二核苷酸-泛醌氧化还原酶介导的呼吸作用，因为只有复合体I的底物、谷氨酸、β-羟基丁酸和α-酮戊二酸介导的呼吸作用降低。由复合体II底物琥珀酸支持的呼吸作用不受任何一种化合物的影响。浓度为50微摩尔的NF分别将氧化谷氨酸的线粒体的状态3和二硝基苯酚解偶联呼吸作用降低至对照的28±1%和25±5%。用氧化谷氨酸的线粒体膜间空间进行的研究表明，NF抑制状态3和状态4的呼吸作用。同时添加超氧化物歧化酶（240微克/毫升）和过氧化氢酶（200微克/毫升）可防止状态3的抑制。这些结果表明，线粒体，特别是电子传递系统的复合体I，是NF毒性的靶点。对呼吸作用的影响可能是由NF氧化还原循环和活性氧中间体的产生介导的，从而导致电子流的干扰。
