Relevance of cytochrome P450 levels in the actions of enflurane and isoflurane in mice: Studies on the haem pathway

1. The effect of the fluorinated ether anaesthetics enflurane and isofluran e in mice on haem metabolism and regulation in different metabolic states, such as depression and induction of cytochrome P450 produced by allylisopro pylacetamide (AIA) and imidazole, respectively, was investigated. 2. Mice previously treated with AIA (350 mg/kg, i.p.) or imidazole (400 mg/ kg, i.p.) received a single dose (1 mL/kg, i.p.) of enflurane or isoflurane and were killed 20 min after anaesthetic administration. 3. Induction of delta-aminolevulinic acid synthetase (ALA-S) activity was f ound, as expected, in animals receiving AIA and also in animals treated wit h AIA plus anaesthesia, but no change in the activity of either porphobilin ogenase (PBGase) or porphobilinogen deaminase (PBG-D) activities was detect ed in these two groups of animals. An additional increase in haem destructi on was observed in the AIA plus isoflurane-treated group. When mice were in jected with imidazol alone or in combination with the anaesthetics, ALA-S a ctivity was increased 50-90% in all groups, but again no change in PBGase o r PBG-D activity was observed. Haem oxygenase was diminished in mice receiv ing imidazole and anaesthesia. 4. In conclusion, neither enflurane nor isoflurane caused additional distur bances in haem metabolism to those produced by AIA or imidazole alone.