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Mercapturic acid formation in the developing rat

P J Baines, H G Bray, S P James

    Xenobiotica; the Fate of Foreign Compounds in Biological Systems
    |November 1, 1977
    PubMed
    Summary
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    Young rats metabolize 1-bromo[1-14C]propane differently than adults, with propylcysteine being a higher proportion of metabolites in younger animals. This age-related difference is linked to developing hepatic glutathione S-alkyltransferase activity.

    Area of Science:

    • Toxicology and Environmental Health
    • Pharmacokinetics and Drug Metabolism
    • Developmental Biology

    Background:

    • The metabolism of xenobiotics can vary significantly with age, impacting toxicity and clearance.
    • Glutathione S-alkyltransferase (GST) is a key enzyme in the detoxification of electrophilic compounds.
    • Understanding age-dependent metabolic profiles is crucial for accurate risk assessment.

    Purpose of the Study:

    • To investigate the age-related excretion patterns of metabolites from 1-bromo[1-14C]propane in rats.
    • To characterize the developmental profile of hepatic glutathione S-alkyltransferase activity in male and female rats.
    • To determine the influence of age on the relative proportions of specific propyl metabolites.

    Main Methods:

    • Rats of various ages were administered 1-bromo[1-14C]propane.

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  • Metabolites in excreted urine were identified and quantified.
  • Hepatic glutathione S-alkyltransferase activity was measured in liver homogenates from male and female rats at different ages.

    • Main Results:

    • Young female rats excreted the same metabolites as adults but in different proportions, with propylcysteine being higher in 5- and 11-day-old rats.
    • Hepatic glutathione S-alkyltransferase activity was low at birth in females, increasing by 30 days, and absent in males until 6 days, then increasing.
    • The ratio of propylmercapturic acid sulphoxide to mercapturic acid excreted was higher in female rats up to 16 days old compared to older animals.

    Conclusions:

    • Age significantly influences the metabolic profile and excretion of 1-bromo[1-14C]propane in rats.
    • Developing hepatic glutathione S-alkyltransferase activity correlates with age-dependent changes in metabolite excretion.
    • These findings highlight the importance of considering developmental stage in toxicological assessments.