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Related Experiment Videos

Nicotinamide-induced hepatic microsomal mixed function oxidase system in rats.

J P Kamat, L M Narurkar, N A Mhatre

    Biochimica Et Biophysica Acta
    |February 21, 1980
    PubMed
    Summary

    Nicotinamide significantly induces key components of the rat liver

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    Area of Science:

    • Biochemistry
    • Pharmacology
    • Toxicology

    Background:

    • The hepatic microsomal mixed function oxidase system is crucial for drug metabolism.
    • Understanding inducers of this system is vital for drug development and toxicology.
    • Nicotinamide is an endogenous metabolite with potential biological activities.

    Purpose of the Study:

    • To investigate the effect of nicotinamide on the hepatic microsomal mixed function oxidase system in male rats.
    • To compare the induction pattern of nicotinamide with other compounds like phenobarbital.

    Main Methods:

    • Administration of nicotinamide, tryptophan, nicotinic acid, and methionine to male rats via intraperitoneal injection.
    • Measurement of hepatic NADPH-cytochrome c reductase, cytochrome P-450, and cytochrome b5 levels.
    • Assay of drug-metabolizing enzyme activities, including arylhydrocarbon hydroxylase, aminopyrine demethylase, and UDP-glucuronosyltransferase.
    • Assessment of protein synthesis using 14C-labelled leucine incorporation and inhibition studies with puromycin.

    Main Results:

    • A single dose of nicotinamide (100 mg/kg) significantly induced all measured components of the hepatic microsomal mixed function oxidase system.
    • Tryptophan, nicotinic acid, and methionine also showed induction of hepatic NADPH-cytochrome c reductase activity.
    • Nicotinamide-induced enzyme activity was linked to increased protein synthesis, inhibited by puromycin.
    • Nicotinamide demonstrated a unique induction pattern distinct from phenobarbital.

    Conclusions:

    • Nicotinamide is a potent inducer of the hepatic microsomal mixed function oxidase system in rats.
    • The induction mechanism involves increased hepatic microsomal protein synthesis.
    • Nicotinamide's effect differs from that of phenobarbital, suggesting a unique pathway of induction.

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