還元的ハロセン代謝におけるcytochrome b5の関与に関する研究
還元的ハロセン代謝におけるcytochrome b5の関与について検討した.マロチレート投与にてcytochrome b5を誘導したラット(マロチレート群)を用いてin vivo及びin vitroにおいて産生された還元的ハロセン代謝産物2-chloro-1,1,1-trifluoroethane (CTE)及び2-chloro-1,1-difluoroethylene(CDE)を測定した.14%O2下1%ハロセン麻酔2時間目の動脈血中CDE/CTEはマロチレート群において対照群に比し有意に高値であった.マロチレート投与により肝ミクロソームにおけるin vitroでのCDE産生及びCDE/CT...
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| Published in | 肝臓 Vol. 29; no. 4; pp. 522 - 527 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本肝臓学会
1988
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.29.522 |
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| Abstract | 還元的ハロセン代謝におけるcytochrome b5の関与について検討した.マロチレート投与にてcytochrome b5を誘導したラット(マロチレート群)を用いてin vivo及びin vitroにおいて産生された還元的ハロセン代謝産物2-chloro-1,1,1-trifluoroethane (CTE)及び2-chloro-1,1-difluoroethylene(CDE)を測定した.14%O2下1%ハロセン麻酔2時間目の動脈血中CDE/CTEはマロチレート群において対照群に比し有意に高値であった.マロチレート投与により肝ミクロソームにおけるin vitroでのCDE産生及びCDE/CTEの有意な上昇を認めた.精製したcytochrome P-450PBを含む再構成系での検討においてcytochrome b5添加でCTE産生が減少しCDE産生が促進された.以上よりcytochrome b5がCTE産生からCDE産生の方向に代謝を変化させることが明らかになった.CTEは有害な遊離ラジカル中間体から,一方CDEはラジカル反応を伴わず産生されるとされており,cytochrome b5がラジカル中間体の遊離を抑制しうることが示された. |
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| AbstractList | 還元的ハロセン代謝におけるcytochrome b5の関与について検討した.マロチレート投与にてcytochrome b5を誘導したラット(マロチレート群)を用いてin vivo及びin vitroにおいて産生された還元的ハロセン代謝産物2-chloro-1,1,1-trifluoroethane (CTE)及び2-chloro-1,1-difluoroethylene(CDE)を測定した.14%O2下1%ハロセン麻酔2時間目の動脈血中CDE/CTEはマロチレート群において対照群に比し有意に高値であった.マロチレート投与により肝ミクロソームにおけるin vitroでのCDE産生及びCDE/CTEの有意な上昇を認めた.精製したcytochrome P-450PBを含む再構成系での検討においてcytochrome b5添加でCTE産生が減少しCDE産生が促進された.以上よりcytochrome b5がCTE産生からCDE産生の方向に代謝を変化させることが明らかになった.CTEは有害な遊離ラジカル中間体から,一方CDEはラジカル反応を伴わず産生されるとされており,cytochrome b5がラジカル中間体の遊離を抑制しうることが示された. |
| Author | 河田, 純男 垂井, 清一郎 田村, 信司 杉山, 俊博 |
| Author_xml | – sequence: 1 fullname: 田村, 信司 organization: 大阪大学医学部第2内科 – sequence: 1 fullname: 河田, 純男 organization: 大阪大学医学部第2内科 – sequence: 1 fullname: 杉山, 俊博 organization: 大阪大学医学部生化学 – sequence: 1 fullname: 垂井, 清一郎 organization: 大阪大学医学部第2内科 |
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| References | 9) Kawata S, Sugiyama T, Imai Y,: Hepatic microsomal cytochrome P-450-dependent N-demethylation of methylguanidine. Biochem Pharmacol 32: 3723-3728, 1983 7) Kawata S, Sugiyama T, Seki K,: Stimulatory effect of cytochrome 1,5 induced by p-nitroanisole and diisopropy1-1,3-dithio1-2-ylidenemalonate on rat liver microsomal drug hydroxylations. J Biochem 92: 305-313, 1982 10) Tamura S, Sugiyama T, Minami Y,: Analysis of debromination of 1,2-dibromoethane by cytochrome P-450-linked hydroxylation systems as observed by bromide electrode. J Biochem 99: 163-171, 1986 4) Rehder K, Cand JF, Alter H,: Halothane biotransformation in man. A quantitative study. Anesthesiology 28: 711-715, 1967 14) Omura T, Sato R: The carbon monoxidebinding pigment of liver microsomes. J Biol Chem 239: 2370-2378, 1964 5) Maiorino RM, Sipes IG, Gandolfi AJ,: Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane. Anesthesiology 54: 383-389, 1981 20) Kawata S, Trzaskos JM, Gaylor JL: Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b5. J Biol Chem 261: 3780-3799, 1986 19) Hildebrandt A, Estabrook RW: Evidence for the participation of cytochrome b5 in hepatic microsomal mixed-function oxidation reactions. Arch Biochem Biophys 143: 66-79, 1971 8) 田村信司,河田純男,乾由明,他:メチルコラントレン誘導性ラット肝チトクロームP450の小葉内分布に関する検討.肝臓 26:1168-1173, 1985 17) Bosterling B, Trudell JR: Production of 5-and 15-hydroperoxyeicosatetraenoic acid from arachidonic acid by halothane-free radicals generated byUV-irradiation. Anesthesiology 60: 209-210, 1984 18) 高橋久雄:慢性エタノール投与ラットにおけるハロセン肝障害に関する実験的研究-特に脂肪過酸化の関与について-.日消誌83: 1168-1175, 1986 3) Poyer JL, McCay PB, Weddle CC,: In vivo spin-trapping of radicals formed during halothane metabolism. Biochem Pharmacol 30: 1517-1519, 1981 2) Brown. BR, Sipes IG: Biotransformation and hepatotoxicity of halothane. Biochem Pharmacol 26: 2091-2094, 1977 16) Lowry OH, Rosebrough NJ, Farr AL,: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265-275, 1951 1) Wright R, Eade OE, Chisholm M,: Controlled prespective study of the effect on liver function of multiple exposure to halothane. Lancet i: 817-820, 1977 15) Oprian DD, Coon MJ: Oxidation-reduction states of FMN and FAD in NADPHcytochrome P-450 reductase during reduction by NADPH. J Biol Chem 257: 8935-8944, 1982 13) Maiorino RM, Sipes IG, Gandolfi AJ,: Quantitative analysis of volatile halothane metabolites in biological tissues by gas chromatography. Chromat Biomed Appl 164: 63-72, 1979 6) Ahr HT, King LJ, Nastainczyk W,: The mechanism of reductive dehalogenation of halothane by liver cytochrome P-450. Biochem Pharmacol 31: 383-390, 1982 11) Yasukochi Y, Masters BSS: Some properties of a detergent-solubilized NADPH-cytochrome c(cytochrome P-450) reductase purified by biospecific affinity chromatography. J Biol Chem 251: 5337-5344, 1986 12) Sugiyama T, Miki N, Yamano T: NADH-and NADPH-dependent reconstituted pnitroanisole o-demethylation system containing cytochrome P-450 with high affnity for cytochrome b5. J Biochem 87: 1457-1467, 1980 |
| References_xml | – reference: 6) Ahr HT, King LJ, Nastainczyk W,: The mechanism of reductive dehalogenation of halothane by liver cytochrome P-450. Biochem Pharmacol 31: 383-390, 1982 – reference: 4) Rehder K, Cand JF, Alter H,: Halothane biotransformation in man. A quantitative study. Anesthesiology 28: 711-715, 1967 – reference: 11) Yasukochi Y, Masters BSS: Some properties of a detergent-solubilized NADPH-cytochrome c(cytochrome P-450) reductase purified by biospecific affinity chromatography. J Biol Chem 251: 5337-5344, 1986 – reference: 10) Tamura S, Sugiyama T, Minami Y,: Analysis of debromination of 1,2-dibromoethane by cytochrome P-450-linked hydroxylation systems as observed by bromide electrode. J Biochem 99: 163-171, 1986 – reference: 2) Brown. BR, Sipes IG: Biotransformation and hepatotoxicity of halothane. Biochem Pharmacol 26: 2091-2094, 1977 – reference: 12) Sugiyama T, Miki N, Yamano T: NADH-and NADPH-dependent reconstituted pnitroanisole o-demethylation system containing cytochrome P-450 with high affnity for cytochrome b5. J Biochem 87: 1457-1467, 1980 – reference: 7) Kawata S, Sugiyama T, Seki K,: Stimulatory effect of cytochrome 1,5 induced by p-nitroanisole and diisopropy1-1,3-dithio1-2-ylidenemalonate on rat liver microsomal drug hydroxylations. J Biochem 92: 305-313, 1982 – reference: 8) 田村信司,河田純男,乾由明,他:メチルコラントレン誘導性ラット肝チトクロームP450の小葉内分布に関する検討.肝臓 26:1168-1173, 1985 – reference: 15) Oprian DD, Coon MJ: Oxidation-reduction states of FMN and FAD in NADPHcytochrome P-450 reductase during reduction by NADPH. J Biol Chem 257: 8935-8944, 1982 – reference: 1) Wright R, Eade OE, Chisholm M,: Controlled prespective study of the effect on liver function of multiple exposure to halothane. Lancet i: 817-820, 1977 – reference: 5) Maiorino RM, Sipes IG, Gandolfi AJ,: Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane. Anesthesiology 54: 383-389, 1981 – reference: 14) Omura T, Sato R: The carbon monoxidebinding pigment of liver microsomes. J Biol Chem 239: 2370-2378, 1964 – reference: 17) Bosterling B, Trudell JR: Production of 5-and 15-hydroperoxyeicosatetraenoic acid from arachidonic acid by halothane-free radicals generated byUV-irradiation. Anesthesiology 60: 209-210, 1984 – reference: 18) 高橋久雄:慢性エタノール投与ラットにおけるハロセン肝障害に関する実験的研究-特に脂肪過酸化の関与について-.日消誌83: 1168-1175, 1986 – reference: 13) Maiorino RM, Sipes IG, Gandolfi AJ,: Quantitative analysis of volatile halothane metabolites in biological tissues by gas chromatography. Chromat Biomed Appl 164: 63-72, 1979 – reference: 16) Lowry OH, Rosebrough NJ, Farr AL,: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265-275, 1951 – reference: 9) Kawata S, Sugiyama T, Imai Y,: Hepatic microsomal cytochrome P-450-dependent N-demethylation of methylguanidine. Biochem Pharmacol 32: 3723-3728, 1983 – reference: 20) Kawata S, Trzaskos JM, Gaylor JL: Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b5. J Biol Chem 261: 3780-3799, 1986 – reference: 3) Poyer JL, McCay PB, Weddle CC,: In vivo spin-trapping of radicals formed during halothane metabolism. Biochem Pharmacol 30: 1517-1519, 1981 – reference: 19) Hildebrandt A, Estabrook RW: Evidence for the participation of cytochrome b5 in hepatic microsomal mixed-function oxidation reactions. Arch Biochem Biophys 143: 66-79, 1971 |
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| SubjectTerms | ハロセン マロチレート 還元的代謝 |
| Title | 還元的ハロセン代謝におけるcytochrome b5の関与に関する研究 |
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