Age-related changes in the metabolism and excretion of allyl isothiocyanate. A model compound for glutathione conjugation.
The objective of this study was to evaluate age-related changes in the in vivo metabolism and excretion of allyl isothiocyanate (AITC), which is used as a model compound to assess glutathione conjugation. AITC is a constituent of oil of mustard and a food additive that has been shown to induce transitional cell papillomas in the urinary bladder of male Fischer rats. Male Fischer rats, ages 3, 16, and 27 months, were dosed orally with 14C-AITC (25 mg/kg). Urine, feces, volatiles, and expired air were collected for 72 hr. Biliary excretion was also examined after iv administration of 10 mg/kg of 14C-AITC. There was no significant difference between these age groups in the percentage of the total dose of AITC eliminated in urine, which is the major route of excretion. The percentage of the dose excreted as volatiles increased in the 27-month animals. These animals also showed a decrease in the production of 14CO2. An age-related decrease in fecal excretion of AITC-derived radioactivity was observed. However, the percentage of the dose excreted in bile increased at 16 months and then decreased in the senescent rats as compared to the 3-month age group. The age-related decrease in 14CO2 production suggests a change in the oxidative metabolism of AITC in senescent animals. However, there was no change in the relative amounts of mercapturic acid excreted in urine, suggesting that glutathione conjugation was unchanged with age.(ABSTRACT TRUNCATED AT 250 WORDS)
Borghoff
S J
SJ
Birnbaum
L S
LS
D000367:Age Factors; D000818:Animals; D001646:Bile / Q000378:metabolism; D005243:Feces / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D017879:Isothiocyanates; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D013861:Thiocyanates / Q000378:metabolism* / Q000652:urine
D017879:Isothiocyanates; D013861:Thiocyanates; C004471:allyl isothiocyanate; D005978:Glutathione