Effect of carbon monoxide on the cytochrome P-450-mediated activation of 4-ipomeanol by the isolated perfused rabbit lung

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Journal of Toxicology and Environmental Health; (USA)

DOI:https://doi.org/10.1080/15287398909531305· OSTI ID:5014732

Trela, B A; Carlson, G P; Turek, J; Rebar, A ^[1]; Mathews, J M ^[2]

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1. Purdue Univ., West Lafayette, IN (USA)
2. Research Triangle Institute, Research Triangle Park, NC (USA)

4-Ipomeanol is a naturally occurring toxin that induces lesions in the lung following its activation to an alkylating metabolite by the pulmonary cytochrome p-450 system. The aim of this study was to determine if an environmentally relevant concentration of carbon monoxide could inhibit the activation of 4-ipomeanol and prevent the associated toxic sequelae in the isolated perfused rabbit lung. The lungs of male New Zealand rabbits were removed and perfused with ({sup 14}C)-4-ipomeanol for 2 h starting with an initial concentration of 0.1 mM. Lungs were ventilated with either air (control) or 7.5% CO/20% O{sub 2}. 4-Ipomeanol-derived covalent binding was identical in the control and carbon monoxide treatment groups. Lungs perfused with 4-ipomeanol and ventilated with air or 7.5% CO/20% O{sub 2} both displayed alveolar type II cell hyperplasia and alveolar macrophage infiltration. Surprisingly, there was no histological evidence of Clara cell damage in any of the 4-ipomeanol-perfused lungs. These results suggest that the isozymes of pulmonary cytochrome p-450 that act in concert to metabolize 4-ipomeanol are relatively insensitive to inhibition by carbon monoxide.

• OSTI ID: 5014732
• Journal Information: Journal of Toxicology and Environmental Health; (USA), Journal Name: Journal of Toxicology and Environmental Health; (USA) Vol. 27:3; ISSN JTEHD; ISSN 0098-4108
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIGENS
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARBON MONOXIDE
CARBON OXIDES
CHALCOGENIDES
ENZYME ACTIVITY
ENZYMES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LUNGS
MAMMALS
MATERIALS
METABOLISM
MIXED-FUNCTION OXIDASES
ORGANS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
OXYGENASES
PERFUSED ORGANS
RABBITS
RESPIRATORY SYSTEM
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VERTEBRATES