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Paraquat inhibits mixed-function oxidation by rat lung.

T K Aldrich, A B Fisher, H J Forman

    Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology
    |April 1, 1983
    PubMed
    Summary
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    Paraquat impairs lung function by depleting NADPH, a crucial coenzyme for detoxification. This study shows paraquat inhibits cytochrome P-450 activity, essential for metabolizing foreign compounds.

    Area of Science:

    • Biochemistry
    • Toxicology
    • Pulmonary Medicine

    Background:

    • Cytochrome P-450 enzymes catalyze critical oxidative reactions in the lung.
    • NADPH is essential for regenerating these enzymes.
    • Paraquat is a herbicide with known lung toxicity.

    Purpose of the Study:

    • To investigate the effect of paraquat on NADPH-dependent cytochrome P-450 activity in isolated rat lungs.
    • To determine if paraquat-induced NADPH depletion impairs mixed-function oxidation.

    Main Methods:

    • Isolated rat lungs were perfused with paraquat.
    • 7-ethoxycoumarin (7-EC) deethylation was measured as an indicator of P-450 activity.
    • NADPH regeneration was manipulated by glucose availability and lactate/pyruvate addition.

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    Main Results:

    • Paraquat significantly inhibited 7-EC deethylation in a dose-dependent manner.
    • Paraquat reduced 7-EC metabolism even when glucose was present, suggesting NADPH depletion.
    • Lactate plus pyruvate partially restored activity in control lungs but not in paraquat-perfused lungs.
    • Paraquat also inhibited p-nitroanisole demethylation, another P-450 reaction.

    Conclusions:

    • Paraquat depletes NADPH in isolated rat lungs, impairing essential mixed-function oxidation.
    • NADPH depletion by paraquat may contribute to its observed lung toxicity.