Abstract
Extrapolation of in vitro data to predict occurrences in vivo is an uncertain process at best. In this study, clearance concepts initially developed to describe elimination of drugs and other substances by kidney and liver have been extended to calculate pulmonary extraction of circulating benzo(a)pyrene 4,5-oxide. Apparent kinetic parameters (Km and Vmax) for pulmonary microsomal epoxide hydrolase and cytosolic glutathione S-transferase were estimated by using in vitro enzyme assays, and whole tissue Vmax values of the two epoxide-metabolizing pathways were determined. From these data, a whole organ extraction ratio for benzo(a)pyrene 4,5-oxide was derived. The calculated extraction ratio (nearly one) was greater than, but in reasonable agreement with, the measured extraction ratio determined by using isolated perfused rabbit lungs exposed to circulating benzo(a)pyrene 4,5-oxide. The actual extraction ratio was 0.64 +/- 0.04 (x +/- S.D.,N = 3), which indicated that the rabbit lung was capable of removing a large percentage of circulating benzo(a)pyrene 4,5-oxide in a single pass through the organ. Therefore, the lung may play an important role in removing and biotransforming circulating arene oxides, as the entire cardiac output passes through the pulmonary capillary bed.
Log in using your username and password
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.