EFFECT OF CHRONIC ANESTHESIA ON THE DRUG-METABOLIZING ENZYME-SYSTEM AND HEME PATHWAY REGULATION

1. The effect of chronic enflurane or isoflurane anesthesia on hepatic heme regulation and the drug-metabolizing system in mice treated or n ot with phenobarbital (PB) was investigated. 2. delta-Aminolevulinic a cid synthetase was induced 50-170% in all cases. Urinary porphyrin pre cursor excretion was also enhanced, but these values were lower when a nimals also received PB. 3. Cytochrome (CYT) P-450 levels were enhance d in animals treated with enflurane whether or not they were given PB. 4. Gluthatione-S-transferase activity was induced by enflurane (138%) or isoflurane (174%), and even more in animals receiving PB also. Sul fatase activity was increased more than 60% with anesthetics. Isoflura ne produced a 50% increase of beta-glucuronidase activity and a 35% di minution of tryptophan pyrrolase.5. The association between anesthetic s and PB produced diverse effects on the metabolizing enzyme system. 6 . Data suggest that both anesthetics, chemically related, could act th rough two different mechanisms, however, with the same final effect: h eme pathway deregulation. (C) 1997 Elsevier Science Inc.