[Hepatotoxicity of halogenated inhalational anesthetics studied in rats hepatocytes].
Effects of 2% halothane, 1.5% sevoflurane, 1.5% enflurane, and 1.2% isoflurane on hepatic dysfunction were studied using rat hepatocytes incubated in media containing 95% or 5% O2. The effects of anesthetics on hepatic perfusion were eliminated by incubation of hepatocytes for 45 minutes with each combination of anesthetic and oxygen concentration. After incubation, viability of hepatocytes was assayed by the LDH latency test. Enzyme (GPT, GOT, LDH) activities, lactate concentration and pyruvate concentration in the incubation medium were measured. The concentrations of adenine nucleotides and inorganic phosphorous in the liver were determined. Anesthetics administered in 95% O2 did not produce significant decreases in viability and enzyme release compared to 95% O2 alone. Halothane, sevoflurane, and isoflurane administered in 5% O2 produced significant decreases in viability and enzyme releases compared to 95% O2 alone. In groups administered 95% O2 there was a significant relationship between viability and energy charge in hepatocytes (P < 0.01). In the 5% O2 groups, there were significant relationships between viability and ATP in hepatocytes (P < 0.01) or L/P ratio in incubation medium (P < 0.01). These results suggest that the combination of anesthetics and hypoxia produce hepatotoxicity. Destruction of energy status might be the cause of hepatotoxicity.
Sameshima
T
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Department of Anesthesiology & Critical Care Medicine, Kagoshima University, School of Medicine.
D000769:Anesthesia, Inhalation; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004734:Energy Metabolism / Q000187:drug effects; D004737:Enflurane / Q000009:adverse effects; D004987:Ethers / Q000009:adverse effects; D006219:Halogens; D006221:Halothane / Q000009:adverse effects; D007530:Isoflurane / Q000009:adverse effects; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008738:Methyl Ethers; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
D004987:Ethers; D006219:Halogens; D008738:Methyl Ethers; D000077149:Sevoflurane; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane