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Minimal biotransformation and toxicity of desflurane in guinea pig liver slices
H N Ghantous1, J Fernando, A J Gandolfi
1Department of Anesthesiology, University of Arizona, College of Medicine, Tucson 85724.
Abstract:
Biotransformation and hepatotoxicity of desflurane were evaluated in the guinea pig liver slice culture system. Liver slices (250-300 microns) were prepared from 600-650-g male Hartley guinea pigs. The slices were incubated in sealed vials in a Krebs-Henseleit buffer at 37 degrees C under 95% O2. Desflurane was vaporized to produce media concentrations of 0.7-2.3 mM. After incubation (3-24 h) viability of the slices was determined (K+ content; protein synthesis secretion) along with the biotransformation of desflurane (F-). Isoflurane (2.3 mM) was included in the studies for comparative purposes. Although desflurane caused a mild concentration-related reduction in slice K+ content (1.1-2.2 mM; 20%-40% of control), the effects were less than those produced by 2.3 mM isoflurane (50% of control). High concentrations of desflurane decreased protein synthesis at the first 9 h of incubation, and isoflurane decreased protein synthesis throughout the incubation period. Neither anesthetic affected protein secretion. The biotransformation of desflurane was minimal with threefold less F- produced from desflurane than isoflurane.
Insights
Desflurane showed minimal biotransformation and less hepatotoxicity than isoflurane in guinea pig liver slices. This suggests desflurane may be a safer anesthetic option with reduced liver injury potential.
Area of Science:
- Anesthesiology
- Hepatology
- Toxicology
Background:
- Inhaled anesthetics like desflurane undergo biotransformation and can cause liver injury.
- Evaluating anesthetic hepatotoxicity is crucial for patient safety.
- Guinea pig liver slice cultures offer a relevant in vitro model for studying drug metabolism and toxicity.
Purpose of the Study:
- To assess the biotransformation and hepatotoxicity of desflurane.
- To compare desflurane's effects with isoflurane in a guinea pig liver slice model.
Main Methods:
- Guinea pig liver slices were incubated with varying concentrations of desflurane (0.7-2.3 mM) or isoflurane (2.3 mM).
- Hepatotoxicity was evaluated by measuring slice viability (K+ content, protein synthesis, and secretion).
- Biotransformation was assessed by quantifying fluoride (F-) ion production.
Main Results:
- Desflurane caused a mild, concentration-dependent reduction in K+ content, less severe than isoflurane.
- High desflurane concentrations transiently decreased protein synthesis, while isoflurane reduced it throughout incubation.
- Biotransformation of desflurane was minimal, producing threefold less fluoride than isoflurane.
Conclusions:
- Desflurane exhibits lower hepatotoxicity compared to isoflurane in this in vitro model.
- The minimal biotransformation of desflurane correlates with its reduced potential for liver injury.
- Desflurane may represent a safer anesthetic choice regarding hepatic effects.