1989 Fiscal Year Final Research Report Summary
Halothane induced Lipid perosidation and Hepatotoxicity
| Project/Area Number |
62570703
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | Hiroshima University |
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Principal Investigator |
FUJII Kohyu Dept. of Anesthesiology, Hiroshima university School of Medicine, Assistant Professor, 医学部, 講師 (60034021)
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| Co-Investigator(Kenkyū-buntansha) |
MUKAIDA Keiko Dept. of Anesthesiology, Hiroshima university School of Medicine, Instructor, 医学部附属病院, 助手 (20182066)
AKITA Susumu Dept. of Anesthesiology, Hiroshima university School of Medicine, Instructor, 医学部, 助手 (40175790)
KIKUCHI Hirosato Dept. of Anesthesiology, Hiroshima university School of Medicine, Associate Prof, 医学部, 助教授 (40034029)
MORIO Michio Dept. of Anesthesiology, Hiroshima university School of Medicine, Chairman and P, 医学部, 教授 (80033950)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Anesthetic / Lipid Peroxydation / Hepatotoxicity / Dehalogenation / Free Radical |
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| Research Abstract |
The mechanism of hepatotoxicity by administration of halothane were studied in vivo and in vitro using guinea pigs.
1. The effects of multiple administration of halothane on the mixed function oxidase system in liver microsomes were investigated and compared between guinea pigs and rats in order to ascertain the difference in sensitivity to halothane. The mixed function oxidase system except for NADPH cytochrome P450 reductase activity was increased in both animals. The inhibition in guinea pigs may have resulted from the microsomal membrane damage induced by the acceleration of lipid peroxidation.
2. The levels of cytochrome P450 and NADPH cytochrome P450 reductase activity were significantly higher in guinea pigs than in rats.No difference between could be demonstrated the two animals in anaerobic dehalogenation activity of halothane per cytochrome P450 in microsomes. Microsomal tocopherol was significantly lower in guinea pigs than in rats. It was increased by multiple exposure to halothane in guinea pigs but remained lower than in rats. Microsomal tocopherol was decreased in rats by multiple exposure. The concentration of reduced glutathion and ascorbic acid was decreased significantly by multiple exposure to halothane in guinea pigs but not in rats.
3. The microsomal lipid peroxidation developed most rapidly and preceded hepatic injury. The effects of administration of metyrapone or N-tert-butyl-phenylnitrone on halothane induced microsomal lipid peroxidation and hepatic damage were investigated. Metyrapone and N-tert-butyl-phenylnitrone inhibited halothane induced lipid peroxidadon and the incidence and severity of hepatic injury.
4. Vitamin E and glutathione reduced pentane formation in the mixture of microsomes and halothane, but did not reduced anaerobic dehalogenation of halothane.
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