Mechanism of hepatotoxicity due to halogenated inhalational anesthetics

1988 Fiscal Year Final Research Report Summary

• Project/Area Number: 62570706
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: 麻酔学
• Research Institution: Kagoshima University
• Principal Investigator: SAMESHIMA Teruko Asistant of Kagoshima University,Faculty of Medicine, 医学部, 助手 (10041328)
• Co-Investigator(Kenkyū-buntansha): MIYAO Junko Asistant of Kagoshima University,Faculty of Medicine, 医学部, 助手 (70107879)
• Project Period (FY): 1987 – 1988
• Keywords: Hepatotoxicity / Halogenated anesthetics / Hepatocyte / Cell metabolism / 酸素濃度

Research Abstract

Isolated rat hepatocytes were used to study the hepatotoxicity of halogenated anesthethics. The authers investigated the effects of halothane, sevoflurane, enflurane and isoflurane on the viability and metabolism of hepatocytes under a stream of 95% oxygen and 5% oxygen respectively. The experimental groups were divided into two groups according to oxygen concentration and then each of groups was further divided into 5 groups in view of the effects of various anesthetics compared with non-anestesia. The hepatocytes were incubated under each stream condition t 37゜C for 45 minutes. The viabilities of hepatocytes decreased in all groups and further decreased in 5% oxygen + anesthetics groups than in 95% oxygen groups. The activities of GOT, GPT and LDN in the incubation medium increased in all groups and more increased in 5% oxygen + anesthetics groups than in 95% oxygen groups. The concentrations of ATP andt he values of energy charge in hepatocytes increased in 95% oxygen groups, but de creased in 5% oxygen groups. The values of ATP/ADP. Pi ratio increased in 95% oxygen groups but unchanged in the other groups. The concentrations of glucose, lactate and pyruvate increased in all groups. The concentrations of glucose and lactate increased in 5% oxygen groups than in 95% oxygen groups, but the concentration of pyruvate increased in 95% oxygen groups than in 5% oxygen groups. The values of L/P ratio increased vigorously in 5% oxygen groups, but decreased in 95% oxygen groups. In 95% oxygen groups there was correlation between viabilities and the values of energy charge. In 5% oxygen groups there were correlations between viabilities and the concentrations of ATP, between viabilities and the values of L/P ratio.There were correlations between GOT,GTP and LHD releases and viability, energy charge, ATP and L/P ration.in summary, in 5% oxygen groups the hepatocyte damage remarkably occurred than in 95% oxygen groups and halogenated anethetics accelerated the damage additionally. It is concluded that the decrease of energy state of hepatocyte and the lactate production might be one of the factors which progress the hepatotoxicity.