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 not with phenobarbital (PB) was investigated. 2. delta-Aminolevulinic acid synthetase was induced 50-170% in all cases. Urinary porphyrin precursor excretion was also enhanced, but these values were lower when animals also received PB. 3. Cytochrome (CYT) P-450 levels were enhanced 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. Sulfatase activity was increased more than 60% with anesthetics. Isoflurane produced a 50% increase of beta-glucuronidase activity and a 35% diminution of tryptophan pyrrolase. 5. The association between anesthetics and PB produced diverse effects on the metabolizing enzyme system. 6. Data suggest that both anesthetics, chemically related, could act through two different mechanisms, however, with the same final effect: heme pathway deregulation.