A selective decrease in the xenobiotic metabolizing activity of rat lungs by nitrogen dioxide exposures

Abstract

Groups of male Wistar rats were continuously exposed to nitrogen dioxide (NO 2) ranging from 1.2 to 15 ppm for 1 or 2 weeks to examine the dose-effect relationship between NO 2 and the xenobiotic metabolizing activity of lung microsomes. The lung cytochrome P-450 decrease significantly after 1-week exposures to 10 and 15 ppm NO 2 and showed a decreasing tendency after 2-week exposures to 6–10 ppm NO 2. On the other hand, the cytochrome b 5, NADPH-cytochrome P-450 reductase and NADH-cytochrome b 5 reductase of lung microsomes were increased concomitant with increase in microsomal proteins during 2-week exposures to 6–10 ppm NO 2. These results show that the lung cytochrome P-450 decreases preferentially upon exposure to NO 2 at higher concentrations. The coumarin hydroxylase activity was the most sensitive to NO 2 exposures among activities metabolizing 4 kinds of xenobiotics examined. The coumarin hydroxylase activity was decreased in a dose-dependent fashion to 67-10% of the control level by 2-week exposures to 1.2–6 ppm NO 2 and became negligible at 10 ppm NO 2. The 7-ethoxycoumarin O-deethylase activity was also decreased to 82-56% of the control level by 2-week exposures to 1.2–6 ppm NO 2 and became a constantly reduced level at 10 ppm NO 2. The benzo[ a]pyrene hydroxylase activity was decreased by exposures to NO 2 above 10 ppm, and the benzphetamine N-demethylase activity also decreased during 2-werk exposures to 6–10 ppm NO 2. These results indicate that exposures to NO 2 above 1.2 ppm cause a consistent and preferential reduction in the activities of coumarin hydroxylase and 7-ethoxycoumarin O-deethylase of lung microsomes in a dose-dependent manner.