Acute moderate hypoxia reduces ethanol elimination in the conscious rabbit

Hypoxic states decrease the catalytic activity of certain enzymes of the cy tochrome P450, leading to decreased clearance of selected xenobiotics. It i s not known whether hypoxia can affect the activity of cytosolic enzymes su ch as liver alcohol dehydrogenase (LADH). This study was carried out to exa mine the effect of experimentally induced acute moderate hypoxia on the kin etics of ethanol and on the catalytic activity of LADH in the conscious rab bit. To this purpose, the kinetics of elimination of ethanol (70 mg/kg intr avenously) were studied in male rabbits (n = 6) kept in an atmosphere with a fractional concentration of O-2 (FiO(2)) of 0.12 for 24 h, and in rabbits (N = 6) breathing room air with a FiO(2) approximate to 0.21 (controls). C ompared with controls, the clearance of ethanol was reduced by 32% (P < 0.0 5) in rabbits exposed to acute moderate hypoxia. In rabbits that consumed a pproximately 6 g/kg/day ethanol in their drinking water for 14 days (n = 6) , acute moderate hypoxia reduced the clearance of ethanol to the same exten t as observed in rabbits receiving a single dose of ethanol. Hypoxia did no t change the in vitro V-max or K-m of LADH. This study demonstrates that ac ute moderate hypoxia reduces the clearance of ethanol following single or m ultiple administrations. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.