Related Experiment Video

Updated: Aug 6, 2026

A Novel Nicotinamide Adenine Dinucleotide Correction Method for Intracellular Ca2+ Measurement with Fura-2-Analog in Live Cells
05:58

A Novel Nicotinamide Adenine Dinucleotide Correction Method for Intracellular Ca2+ Measurement with Fura-2-Analog in Live Cells

Published on: September 20, 2019

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

L O Lim, R Bortell, A H Neims

    Toxicology and Applied Pharmacology
    |July 1, 1986
    PubMed

    Insights

    Nitrofurantoin (NF) and nitrofurazone (NZ) disrupt mouse liver mitochondrial respiration, primarily targeting Complex I. This toxicity may stem from reactive oxygen species generated by NF redox cycling.

    Area of Science:

    • Biochemistry
    • Mitochondrial Physiology
    • Toxicology

    Background:

    • Nitrofurantoin (NF) and nitrofurazone (NZ) are antimicrobial agents.
    • Their effects on cellular respiration, particularly mitochondrial function, are not fully elucidated.
    • Understanding their toxic mechanisms is crucial for safe therapeutic use.

    Purpose of the Study:

    • To investigate the impact of NF and NZ on isolated mouse liver mitochondria respiration.
    • To identify the specific site of action within the mitochondrial electron transport chain.
    • To explore the role of reactive oxygen species in NF-induced mitochondrial toxicity.

    Main Methods:

    • Isolated mouse liver mitochondria were used to assess respiration.
    • Complex I and Complex II substrates were employed to determine the site of inhibition.
    • Mitoplasts were utilized to study the effects on different respiratory states.
    • Superoxide dismutase and catalase were added to investigate the role of reactive oxygen species.

    Main Results:

    • NF and NZ significantly inhibited mitochondrial respiration, while other nitroaromatic compounds did not.
    • The primary target of NF was Complex I (NADH-ubiquinone oxidoreductase), evidenced by decreased respiration with Complex I substrates.
    • NF inhibited both state 3 and state 4 respiration, an effect mitigated by antioxidants, suggesting reactive oxygen species involvement.

    Conclusions:

    • Mitochondria, specifically Complex I of the electron transport chain, are a key target for nitrofurantoin toxicity.
    • NF-induced mitochondrial dysfunction may involve redox cycling and the generation of reactive oxygen intermediates.
    • These findings provide insights into the cellular mechanisms underlying nitrofurantoin's adverse effects.

    More Related Videos

    NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases10:24

    NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases

    Published on: June 30, 2019

    Real-Time Measurement of the Mitochondrial Bioenergetic Profile of Neutrophils09:39

    Real-Time Measurement of the Mitochondrial Bioenergetic Profile of Neutrophils

    Published on: June 2, 2023

    Related Concept Videos

    ATP Synthase: Mechanism01:48

    ATP Synthase: Mechanism

    In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
    Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

    Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

    Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...