Demonstration of Halothane-induced Hepatic Lipid Peroxidation in Rats by Quantification of Flourine2-Isoprostanes.
Awad, Joseph A. MD; Horn, Jean-Louis MD; Roberts II, L. Jackson MD; Franks, John J. MD
84(4):910-916, April 1996.
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Background: Halothane can be reductively metabolized to free radical intermediates that may initiate lipid peroxidation. Hypoxia and phenobarbital pretreatment in Sprague-Dawley rats increases reductive metabolism of halothane. Flourine2 -isoprostanes, a novel measure of lipid peroxidation in vivo, were used to quantify halothane-induced lipid peroxidation in rats.
Methods: Rats were exposed to 1% halothane at 21% or 14% Oxygen2 for 2 h. Pretreatments included phenobarbital, isoniazid, or vehicle. Rats also were exposed to halothane, enflurane, and desflurane at 21% Oxygen2. Lipid peroxidation was assessed by mass spectrometric quantification of Flourine2 -isoprostanes.
Results: Exposure of phenobarbital-pretreated rats to 1% halothane at 21% Oxygen2 for 2 h caused liver and plasma Flourine2 -isoprostane concentrations to increase fivefold compared to nonhalothane control rats. This halothane-induced increase was enhanced by 14% Oxygen sub 2, but hypoxia alone had no significant effect. Alanine aminotransferase activity at 24 h was significantly increased only in the 1% halothane/14% Oxygen2 group. The effect of cytochrome P450 enzyme induction on halothane-induced Flourine2 -isoprostane production and liver injury was determined by comparing the effects of isoniazid and phenobarbital pretreatment with no pretreatment under hypoxic conditions. Halothane caused 4- and 11-fold increases in plasma and liver Flourine2 -isoprostanes, respectively, in non-pretreated rats, whereas isoniazid pretreatment had no effect. Phenobarbital pretreatment potentiated halothane-induced lipid peroxidation with 9- and 20-fold increases in plasma and liver Flourine2 -isoprostanes, respectively. Alanine aminotransferase activity was increased only in this group. At ambient oxygen concentrations, halothane but not enflurane or desflurane, caused Flourine2 -isoprostanes to increase.
Conclusions: Specific halothane-induced lipid peroxidation was demonstrated in Sprague-Dawley rats using quantification of Flourine2 -isoprostanes and was increased by hypoxia and phenobarbital pretreatment, but not isoniazid pretreatment.
(C) 1996 American Society of Anesthesiologists, Inc.