Effect of carbon monoxide on the cytochrome P-450-mediated metabolism of aniline and p-nitroanisole in the isolated perfused rabbit lung.
Carbon monoxide (CO), an environmental pollutant, inhibits the cytochrome P-450-mediated metabolism of xenobiotics in vitro. In recent years, the importance of the lung in the metabolic disposition of certain airborne and systemically administered xenobiotics has been demonstrated. The purpose of this investigation was to establish a threshold for the CO-induced inhibition of cytochrome P-450-mediated activities in the isolated perfused rabbit lung and to determine if these reactions are equally sensitive to this toxicant in this model. Neither the mixed-function oxidase-mediated hydroxylation nor the acetylation of aniline was altered by exposure to 7.5% CO/20% O2 for 2.5 h in the isolated perfused rabbit lung. p-Nitroanisole O-demethylation by isolated rabbit lungs ventilated with 7.5% CO/20% O2 was significantly decreased (approximately 37%) in comparison to controls. That these reactions are not similarly influenced by carbon monoxide may indicate that the constitutive isozymes of cytochrome P-450 in the rabbit lung are differentially sensitive to CO-induced inhibition.
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
B A
BA
Trela
G P
GP
Carlson
P R
PR
Mayer
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D000840:Anisoles / Q000378:metabolism*; D002248:Carbon Monoxide / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion / Q000295:instrumentation / Q000379:methods; D011817:Rabbits
D000814:Aniline Compounds; D000840:Anisoles; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; C005306:4-nitroanisole; C023650:aniline