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Decrease in calcium carbimide (calcium cyanamide)-induced inhibition of rat hepatic aldehyde dehydrogenases by

C W Loomis, J F Brien

    Canadian Journal of Physiology and Pharmacology
    |May 1, 1984
    PubMed
    Summary

    Calcium carbimide (CC) and ethanol interact to affect liver enzyme activity. Repeated ethanol doses after CC reduce acetaldehyde levels and enhance liver aldehyde dehydrogenase recovery, suggesting a displaceable inhibitor.

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    Area of Science:

    • Pharmacology
    • Biochemistry
    • Toxicology

    Background:

    • Calcium carbimide (CC) is used in alcohol aversion therapy.
    • Ethanol metabolism produces toxic acetaldehyde, primarily metabolized by aldehyde dehydrogenase (ALDH).
    • Understanding the interaction between CC and ethanol is crucial for managing adverse effects.

    Purpose of the Study:

    • To investigate the effect of CC and ethanol dosing on blood acetaldehyde levels.
    • To examine the impact of CC and ethanol on hepatic aldehyde dehydrogenase (ALDH) activity.
    • To explore the recovery patterns of ALDH following CC and ethanol administration.

    Main Methods:

    • Adult male rats were administered calcium carbimide (CC) followed by one or two doses of ethanol.
    • Blood ethanol and acetaldehyde concentrations were measured using area-under-curve data.

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  • Hepatic aldehyde dehydrogenase activity was assessed in various liver fractions (mitochondrial, cytosolic, microsomal) at specific time intervals.

    • Main Results:

    • Blood acetaldehyde concentrations were significantly lower for the second ethanol dose when administered after CC.
    • Inhibition of both low Km and high Km hepatic ALDH activity was significantly less in rats receiving two ethanol doses compared to one dose or no ethanol after CC.
    • Recovery of hepatic ALDH activity was augmented in rats treated with CC and two ethanol doses.

    Conclusions:

    • The interaction between CC and ethanol leads to increased acetaldehyde levels.
    • Repeated ethanol administration following CC can enhance the recovery of hepatic aldehyde dehydrogenase activity.
    • The findings suggest the presence of a displaceable enzyme inhibitor derived from CC that affects ALDH activity.