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Interaction of induction, ontogenetic development and liver regeneration on the monooxygenase level

W Klinger, E Karge

    Experimental Pathology
    |January 1, 1987
    PubMed

    Insights

    Liver regeneration after surgery impacts drug metabolism in young and adult rats. While initial recovery occurs, surgical stress and regeneration interact with drug-metabolizing enzyme activity, showing age-dependent effects.

    Area of Science:

    • Pharmacology
    • Hepatology
    • Developmental Biology

    Background:

    • Surgical procedures like 2/3 hepatectomy (HX) and sham operations (SO) affect liver mass and function.
    • Understanding the interplay between liver regeneration, ontogenetic development, and drug metabolism is crucial.
    • Age-dependent responses to surgical stress and induction of drug-metabolizing enzymes require investigation.

    Purpose of the Study:

    • To investigate the effects of hepatectomy and sham operation on liver mass and drug metabolism in young (10-day-old) and adult (60-day-old) rats.
    • To examine the impact of phenobarbital (PB) and beta-naphthoflavone (BNF) induction on drug metabolism following surgery.
    • To elucidate how regeneration, induction, and ontogenetic development interact and influence monooxygenase activity.

    Main Methods:

    • Performed 2/3 hepatectomy (HX) and sham operations (SO) on 10- and 60-day-old male Wistar rats.
    • Measured liver dry mass, ethylmorphine N-demethylation (EN), and ethoxycoumarin O-deethylation (EO) at various time points post-surgery.
    • Assessed inducibility of cytochrome P-450 (P-450) and monooxygenase activities by phenobarbital (PB) and beta-naphthoflavone (BNF).

    Main Results:

    • Both SO and HX reduced liver mass initially, with greater impact after HX.
    • Drug metabolism (EN and EO) was decreased by SO and HX, more significantly after HX.
    • Young rats showed recovery of metabolic function within 14 days, with EN exceeding controls after 3 weeks; adult rats showed prolonged depression of EN and EO after SO.

    Conclusions:

    • Liver regeneration and surgical stress can be superimposed on ontogenetic development, influencing drug metabolism differently based on age.
    • Induction of drug-metabolizing enzymes can enhance ontogenetic development, and regeneration can be modulated by induction.
    • Different monooxygenases exhibit differential control during these complex developmental and regenerative processes.

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