Effect of carbon monoxide on xenobiotic metabolism in the isolated perfused rabbit lung
It was the aim of this study to determine the level and duration of CO exposure necessary to alter mixed function oxidase-mediated activity in the intact lung and to determine the magnitude of this effect. The effect of CO on the mixed function oxidase-mediated activities of aminopyrine, aniline, 4-ipomeanol and p-nitroanisole in isolated perfused rabbit lungs (IPRL) was investigated. Several concentrations of CO were evaluated for their effect on cytochrome P-450-mediated activity in the lung. Both artificial medium and whole blood were utilized as recirculating perfusates. Monomethyl-4-aminoantipyrine was the major metabolite of aminopyrine produced by in vitro hepatic and pulmonary preparations and by the intact lung. Ventilation of isolated rabbit lungs with 7.5% CO for 2.5 hours caused a 40% decrease in the rates of metabolism of both aminopyrine and p-nitroanisole. This level of CO exposure did not alter the cytochrome P-450-mediated metabolism of aniline nor 4-ipomeanol in the intact lung. Aminopyrine metabolism in isolated rabbit lungs perfused with whole blood was also decreased following the administration of 7.5% CO suggesting that the hemoglobin in whole blood affords no protection against CO-induced inhibition of mixed function oxidase activity in the intact lung. The isozyme of cytochrome P-450 which preferentially metabolizes aminopyrine and p-nitroanisole may be more sensitive to CO-induced inhibition than the form(s) which metabolize aniline and 4-ipomeanol.
- Research Organization:
- Purdue Univ., Lafayette, IN (USA)
- OSTI ID:
- 5400398
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CARBON MONOXIDE
BIOLOGICAL EFFECTS
MIXED-FUNCTION OXIDASES
ENZYME ACTIVITY
XENOBIOTICS
METABOLISM
ANTIPYRINE
BLOOD
LUNGS
PERFUSED ORGANS
RABBITS
ANIMALS
ANTIPYRETICS
AZOLES
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CARBON COMPOUNDS
CARBON OXIDES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHALCOGENIDES
DRUGS
ENZYMES
HETEROCYCLIC COMPOUNDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
OXYGENASES
PYRAZOLES
PYRAZOLINES
RESPIRATORY SYSTEM
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology