Binding of halothane-free radicals to fatty acids following UV irradiation.
Bosterling-B; Trevor-A; Trudell-JR
Anesthesiology 1982 May; 56(5):380-384
An attempt was made to establish the existence of halothane free radicals and determine their structure by two techniques. Halothane (151677) was first irradiated with ultraviolet light in the presence of methyl-oleate. If a halothane free radical was present it would be expected to add preferentially to the double bond of methyl- oleate to produce a substituted saturated methyl stearate, for example, with the 1-chloro-2,2,2-trifluoroethyl substituent added to either the 9 or 10 position of the fatty acid chain. The authors also endeavored to trap halothane free radicals by exposing halothane vapor diluted in argon to an ultraviolet light source and then bubbling it into a solution of a free radical spin trap. This spin trap, phenyl-t-butylnitrone was able to react rapidly with free radicals and retain the unpaired electron for a time sufficient to observe a free radical spectrum with an electron paramagnetic resonance spectrometer. If the initial radical spin trap adduct were stable, hyperfine splittings in the electron paramagnetic resonance spectrum would allow interpretation of the structure of the free radical. The results indicated that the addition of a 1- chloro-2,2,2-trifluoroethyl radical to the double bond of a fatty acid chain was a reasonable hypothesis for the initiation of halothane metabolite binding to phospholipids and subsequent damage to the endoplasmic reticulum. The authors urged caution in the use of ultraviolet light or other ionizing radiation in the presence of halothane.
NIOSH-Publication; NIOSH-Grant; Grants-other; Anesthetics; Radiation-hazards; Metabolic-study; Pulmonary-system-disorders; Ultraviolet-radiation; Halogenated-hydrocarbons;
Author Keywords: Anesthetics; volatile; halothane; Biotransformation; fluorometabolites; Liver; toxicity; Membrane; lipid peroxidation; phospholipids; Toxicity; hepatic; metabolites
Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
Other Occupational Concerns; Grants-other; Pulmonary-system-disorders
Stanford University, Stanford, California