Induction of the monooxygenase enzyme system in human lung

In the present study, lung tissue of patients suffering from tuberculosis and undergoing thoracic surgery was investigated. All these patients were treated prior to surgery by an anti-tuberculous drug regimen, including rifampicin, for 3-6 months. Patients having non-malignant lung disease served as controls. In the lung tissue obtained, 7-ethoxycoumarin-0-deethylase as a substrate of monooxygenase activity, epoxide hydrolase and glutathione-S-transferase were measured. Monooxygenase activity increased from 0.62 + 0.10 pmol mg protein-1 min-1 in the control group to 1.55 +/- 0.34 pmol mg protein-1 min-1 (P less than 0.02) following anti-tuberculous drug treatment, while the other enzymes remained unchanged. Rifampicin, a potent inducer of hepatic metabolism in man, seems a likely cause for the changes in monooxygenase activity, since for other anti-tuberculous drugs no enzyme-inducing effect has so far been reported in any tissue in man. In addition, the activity of the disease seems to be of great importance for the extent of induction. Thus, in patients with active tuberculosis, higher monooxygenase activities were found, compared to those with inactive disease (1.92 +/- 0.53 vs. 0.99 +/- 0.24 pmol mg protein-1 min-1), both showing even higher values than controls.