An investigation into the hepatic cytochrome P-450 catalysed metabolism of the anaesthetic fluroxene (2,2,2-trifluoroethyl vinyl ether).
The role of the different cytochromes P-450 in the metabolism of the anaesthetic agent fluroxene, and the mechanism of production of toxic effects seen after pre-treatment of the animals with pehnobarbital prior to anaesthesia, have been investigated. Male rats were anaesthetized with fluroxene, or with 2,2,2-trifluroethyl ethyl ether, or with ethyl vinyl ether in an attempt to ascertain the in vivo toxic effects of the three anaesthetic agents. The resultant hepatic histology is reported. A study of the binding and metabolism of fluroxene by isolated rat hepatic microsomes was also made. We conclude that it is elevated levels of cytochrome P-450 which potentiate the toxicity of fluroxene anaesthesia in phenobarbital treated animals and that cytochrome P-448 does not bind or metabolize fluroxene. The potential toxicity of the fluroxene molecule is considered to reside in the trifluoroethyl moiety, while the vinyl group of fluroxene appears to play a role in the observed liver damage.
D000502:Allylisopropylacetamide / Q000494:pharmacology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004986:Ether / Q000031:analogs & derivatives; D004987:Ethers / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D003580:Cytochromes; D004987:Ethers; D004986:Ether; D000502:Allylisopropylacetamide; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital