title: Sevoflurane is biotransformed by guinea pig liver slices but causes minimal cytotoxicity.
abstract: Guinea pig liver slices were used to evaluate the biotransformation and hepatotoxic potential of sevoflurane. Precision-cut liver slices (250-300 microns thick) were incubated in sealed roller vials in buffer at 37 degrees C under 95% O2. Sevoflurane was added to produce 0.9 or 2.1 mM medium concentrations. After incubation (6-24 h), the intracellular K+ content and protein synthesis were determined, along with the defluorination of sevoflurane. Isoflurane was included for comparative purposes. Sevoflurane (2.1 mM) and isoflurane (2.3 mM) had no effect on slice K+ content, but both anesthetics depressed protein synthesis. The biotransformation of sevoflurane was maximal at 95% O2, with threefold more F- produced from sevoflurane than isoflurane. Sevoflurane appears to have a minimal effect on the guinea pig liver slices, which is consistent with in vivo studies in which minimal or no hepatotoxicity has been observed.
authors.affiliation: Department of Anesthesiology, College of Medicine, University of Arizona, Tucson 85724.
authors.forename: H N
authors.initials: HN
authors.lastname: Ghantous
authors.forename: J
authors.initials: J
authors.lastname: Fernando
authors.forename: A J
authors.initials: AJ
authors.lastname: Gandolfi
authors.forename: K
authors.initials: K
authors.lastname: Brendel
mesh_terms: D000433:1-Propanol / Q000494:pharmacology; D000777:Anesthetics / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury; D004987:Ethers / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D006168:Guinea Pigs; D007530:Isoflurane / Q000494:pharmacology; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008738:Methyl Ethers; D011188:Potassium / Q000378:metabolism; D020005:Propanols; D000077149:Sevoflurane; D013997:Time Factors; D006845:Hydrocarbons, Fluorinated
chemical_list: D000433:1-Propanol; D000777:Anesthetics; D004987:Ethers; D007530:Isoflurane; D008738:Methyl Ethers; D011188:Potassium; D020005:Propanols; D000077149:Sevoflurane; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated