Effect of carbon monoxide on the cytochrome P‐450‐mediated metabolism of aniline andp‐nitroanisole in the isolated perfused rabbit lung

Abstract

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 (‐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.