| Project/Area Number |
06671525
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
FUJII Kohyu Hiroshima University, School of Medicine, Assistant Professor, 医学部, 講師 (60034021)
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| Co-Investigator(Kenkyū-buntansha) |
YUGE Osafumi Hiroshima University, School of Medicine, Professor, 医学部, 教授 (40034128)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Anesthetics / Enhancement / Isoflurane / Halothane / enflurane / Sevoflurane / Carbon Tetrachloride / 代謝活性 |
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| Research Abstract |
1) The effects of isoflurane on the reductive metabolism of halothane to produce in the liver microsomes of guinea pig were examined. Isoflurane had no effect on NADPH-cytochrome P450 reductase. Isoflurane enhances cytochrome p450 reduction by NADPH.Isoflurane enhances the formation of an intermediate complex. Isoflurane accerelated the anaerobic dehalogenation of halothane to produce chlorodifluoroethylene and chlorotifluoroethane while inhibited the aerobic dehalogenation of halothane to produce trifluoroacetic acid in the guinca pig liver nicrosomes. We conclude that isoflurane interact with cytochrome p450 to enhance cytochrome p450 reduction, causing of enhancement of reductive dehalogenation of halothane.
2) The in vitro effects of isoflurane on aniline hydroxylation and aminopyrine N-demethylation were investigated with guinea pig liver microsomes to assess the role of isoflurane on oxidative drug metabolism through the hepatic mixed function oxidase system.
p-Aminophenol and form
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aldehyde were measured spectrophtometrically as metabolic products of aniline hydroxylation and aminopyrine N-demethylation, respectively, where the reaction mixture consisted of microsomal suspension, NADPH,aminopyrine or aniline and with or without isoflurane. The rate of cytochrome P-450 reduction by NADPH affected in the presence of isoflurane was investigated by spectrometric measurement of CO-cytochrome P-450 complex formation at various times.
Due to the addition of isoflurane, the Vmax values for aniline hydroxylation evidently increased except in high isoflurane concentration (3.33mM) and for aminopyrine N-demethylation the value was significantly low only in presence of high isoflurane concentration, whereas the Km values significantly decreased in aniline hydroxylation and increased in aminopyrine N-demethylation, and isoflurane also accelerated the rate of cytochrome P-450 reduction by NADPH.
These results reflect the inhibition of aminopyrine N-demethylation and activation of aniline hydroxylation in the presence of isoflurane as a consequence of isoflurane accelerated cytochrome P-450 reduction by NADPH and/or drug-enzyme binding properties, and may have implications on the metabolism of perioperatively administered drugs during isoflurane anesthesia.
3) The order of affectivity of volatile anesthetics on the guiea pig liver microsomal electron transport system were isoflurane>ebflurane>halothane>sevoflurane. Less
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