Nitrofurantoin inhibition of mouse liver mitochondrial respiration involving NAD-linked substrates

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalase / pharmacology
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Nitro Compounds / pharmacology
  • Nitrofurantoin / pharmacology*
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Oxygen Consumption / drug effects*
  • Substrate Specificity
  • Superoxide Dismutase / pharmacology


  • Nitro Compounds
  • Nitrofurantoin
  • Catalase
  • Superoxide Dismutase