Effects of helium-oxygen and hyperbaric helium-oxygen environment on drug-metabolizing enzyme activity in rat liver

The effects of room-air normoxic (22 degrees C +/- 1 degree C), 1.2-ATA He-O2 (400 mmHg PO2, 29.0 degree C +/- 1 degree C), and 21-ATA He-O2 (400 mmHg PO2, 32.5 degrees C +/- 1 degree C) environments were investigated on the activity of drug-metabolizing enzyme systems in rat liver, as monitored by O-dealkylation and N-dealkylation reactions. Continuous exposure of rats to both He-O2 environments for 12 days significantly increased the in vitro activity of drug-metabolizing enzymes in liver preparations. The increase in the in vitro O-dealkylation of p-nitroanisole based on product formed X mg protein-1 X 20 min-1 was 32.2% (P less than 0.05) between normoxic animals and those exposed to 1.2 ATA He-O2, and 24.4% (P less than 0.01) in animals exposed to between 1.2 and 21 ATA He-O2. A significant increase of 48.8% (P less than 0.001) was noted between normoxic animals and those exposed to 21 ATA He-O2. Similar differences were noted if the data were expressed on the basis of 200 mg liver wet wt. The N-dealkylation of morphine based on product formed X mg protein-1 X 20 min-1 was significantly increased between animals kept at normoxic and at 1.2-ATA He-O2 conditions (17.6%, P less than 0.05) and between animals kept at normoxic and at 21 ATA He-O2 conditions (28.2%, P less than 0.05). No significant differences for N-dealkylation of morphine were noted between animal groups at 1.2 and those at 21 ATA He-O2 nor between any animal groups for N-dealkylation of cocaine.