Alterations in conjugation reactions with age and its influence on xenobiotic sensitivity in senescent animals

Thesis/Dissertation · Thu Jan 01 04:00:00 EST 1987

OSTI ID:7160793

Borghoff, S J

Altered ability to metabolize drugs or xenobiotics with age have been suggested to contribute to the enhanced sensitivity of the elderly to various compounds. To investigate altered conjugation reactions with age, model compounds were selected that have previously been shown to depend on conjugation for their excretion. Allyl isothiocyanate (AITC) and 4,4'-thiobis-(6-t-butyl-m-cresol) (TBBC) were used to evaluate glutathione conjugation and glucuronidation, respectively. AITC is excreted mainly in urine as a mercapturic acid which is formed subsequent to the conjugation of glutathione with AITC. We administered /sup 14/C-AITC to male F344 rats 3, 16, and 27 months of age and measured total radioactivity excreted. Metabolites were evaluated in both urine and bile. TBBC was selected to evaluate glucuronidation with age since it forms a glucuronide of the parent without any prior oxidation. TBBC was administered to male rats 2.5, 16, and 26 months of age. TBBC-derived radioactivity eliminated in urine, feces and bile decreased with age. We hypothesized that this age-related decrease in TBBC excretion would lead to a build up of TBBC thereby resulting in enhanced toxic effects. TBBC toxicity was evaluated with age and no differences in toxicity were observed.

• Research Organization: North Carolina Univ., Chapel Hill (USA)
• OSTI ID: 7160793
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AGE DEPENDENCE
ANIMALS
AROMATICS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CRESOLS
DRUGS
FECES
GLUTATHIONE
HYDROXY COMPOUNDS
ISOTHIOCYANATES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
PHENOLS
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
TOXICITY
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES