Reduction of hepatic tetrahydrofolate and inhibition of exhalation of /sup 14/CO/sub 2/ formed from (dimethylamino-/sup 14/C)aminopyrine in nitrous oxide-treated rats
The exhalation of /sup 14/CO/sub 2/ after the administration of (dimethylamino-/sup 14/C)aminopyrine to an organism is assumed to reflect the demethylation of aminopyrine by hepatic mixed-function oxidase activity. The last step in the pathway, i.e., formate oxidation, is dependent upon tetrahydrofolate; thus, factors which alter hepatic tetrahydrofolate potentially may modify /sup 14/C-aminopyrine metabolism to /sup 14/CO/sub 2/ in vivo. Exposure of rats to nitrous oxide (N/sub 2/O) produces a significant reduction in hepatic tetrahydrofolate as a result of the inhibition of 5-methyltetrahydrofolate:homocysteine methyltransferase activity (E.C. 2.1.1.13). In the present study, exposure of rats to N/sub 2/O/O/sub 2/ (1:1) for 4 hr prior to the administration of /sup 14/C-aminopyrine (40 or 400 mumoles per kg) produced a 60% reduction in the peak rate of /sup 14/CO/sub 2/ exhalation and a 45% decrease in the total /sup 14/CO/sub 2/ exhaled within 2 hr. Aminopyrine (400 mumoles per kg) administration to air-breathing rats did not affect the level of urinary formate, but exposure to N/sub 2/O produced a 40-fold increase. Aminopyrine administration to N/sub 2/O-exposed rats produced a 75% increase in urinary formate as compared to rats treated with N/sub 2/O alone.
- Research Organization:
- Univ. of Iowa, Iowa City
- OSTI ID:
- 5776236
- Journal Information:
- Hepatology (N.Y.); (United States), Vol. 4:5
- Country of Publication:
- United States
- Language:
- English
Similar Records
Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration
Effect of glutathione depletion on UCO2 evolution from ( UC)methyl-labeled aminopyrine in intact rats
Related Subjects
CARBON 14 COMPOUNDS
EXHALATION
CARBON DIOXIDE
FOLIC ACID
BIOCHEMISTRY
NITROUS OXIDE
BIOLOGICAL EFFECTS
TRANSFERASES
INHIBITION
AMINES
FORMATES
RATS
AMINO ACIDS
ANIMALS
AROMATICS
AZAARENES
CARBON COMPOUNDS
CARBON OXIDES
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CHALCOGENIDES
CHEMISTRY
CLEARANCE
DRUGS
ENZYMES
EXCRETION
HEMATINICS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PTERIDINES
RODENTS
VERTEBRATES
VITAMIN B GROUP
VITAMINS
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)