Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a-knockout mice

Junitsu Ito, Noriyuki Otsuki, Xuhong Zhang, Tasuku Konno, Toshihiro Kurahashi, Motoko Takahashi, Mayumi Yamato, Yuta Matsuoka, Ken-Ichi Yamada, Satoshi Miyata, Junichi Fujii

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

Aims Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, is highly expressed in the liver and is involved in both the detoxification of carbonyl compounds and ascorbic acid biosynthesis. By comparison with wild-type mice, Akr1a-knockout (Akr1a-/-) mice and human Akrla-transgenic (Akr1atg/+) mice experience different anesthetic actions from pentobarbital - prolonged in Akr1a-knockout (Akr1a -/-) mice and shortened in human Akrla-transgenic (Akr1a tg/+) mice. Main methods We investigated this alteration in the anesthetic efficacy of pentobarbital in Akr1a genetically modified mice. Key findings Neither the cytosolic protein of wild-type mouse liver nor purified rat AKR1A directly reduced pentobarbital. Ascorbic acid administration neutralized the prolonged duration of the loss of the righting reflex (LORR) in Akr1a -/- mice, but preincubation of pentobarbital with ascorbic acid prior to administration did not change the anesthetic effect. Those results indicated that ascorbic acid does not directly reduce pentobarbital. Enzymatic activities and levels of the proteins of some cytochrome P450s that make up a potent detoxification system for pentobarbital showed no changes in the genetically modified mice examined. Thus, ascorbic acid also had no effect on the detoxification system in the liver. The prolonged duration of LORR in the Akr1a-/- mice caused by pentobarbital and the neutralization of the anesthetic effect by ascorbic acid together with other results imply that ascorbic acid alters the responses of the neuronal system to anesthetics. Significance Pentobarbital action is increased under conditions of ascorbic acid deficiency, and this may have to be taken into account when anesthetizing malnourished patients.

元の言語英語
ページ(範囲)1-8
ページ数8
ジャーナルLife Sciences
95
発行部数1
DOI
出版物ステータス出版済み - 1 24 2014

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Pentobarbital
Knockout Mice
Ascorbic Acid
Anesthetics
Detoxification
Liver
Righting Reflex
Ascorbic Acid Deficiency
Aldehyde Reductase
Carbonyl compounds
Biosynthesis
Cytochromes
Transgenic Mice
Rats
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

これを引用

Ito, J., Otsuki, N., Zhang, X., Konno, T., Kurahashi, T., Takahashi, M., ... Fujii, J. (2014). Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a-knockout mice. Life Sciences, 95(1), 1-8. https://doi.org/10.1016/j.lfs.2013.12.004

Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a-knockout mice. / Ito, Junitsu; Otsuki, Noriyuki; Zhang, Xuhong; Konno, Tasuku; Kurahashi, Toshihiro; Takahashi, Motoko; Yamato, Mayumi; Matsuoka, Yuta; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi.

:: Life Sciences, 巻 95, 番号 1, 24.01.2014, p. 1-8.

研究成果: ジャーナルへの寄稿記事

Ito, J, Otsuki, N, Zhang, X, Konno, T, Kurahashi, T, Takahashi, M, Yamato, M, Matsuoka, Y, Yamada, K-I, Miyata, S & Fujii, J 2014, 'Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a-knockout mice', Life Sciences, 巻. 95, 番号 1, pp. 1-8. https://doi.org/10.1016/j.lfs.2013.12.004
Ito, Junitsu ; Otsuki, Noriyuki ; Zhang, Xuhong ; Konno, Tasuku ; Kurahashi, Toshihiro ; Takahashi, Motoko ; Yamato, Mayumi ; Matsuoka, Yuta ; Yamada, Ken-Ichi ; Miyata, Satoshi ; Fujii, Junichi. / Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a-knockout mice. :: Life Sciences. 2014 ; 巻 95, 番号 1. pp. 1-8.
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abstract = "Aims Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, is highly expressed in the liver and is involved in both the detoxification of carbonyl compounds and ascorbic acid biosynthesis. By comparison with wild-type mice, Akr1a-knockout (Akr1a-/-) mice and human Akrla-transgenic (Akr1atg/+) mice experience different anesthetic actions from pentobarbital - prolonged in Akr1a-knockout (Akr1a -/-) mice and shortened in human Akrla-transgenic (Akr1a tg/+) mice. Main methods We investigated this alteration in the anesthetic efficacy of pentobarbital in Akr1a genetically modified mice. Key findings Neither the cytosolic protein of wild-type mouse liver nor purified rat AKR1A directly reduced pentobarbital. Ascorbic acid administration neutralized the prolonged duration of the loss of the righting reflex (LORR) in Akr1a -/- mice, but preincubation of pentobarbital with ascorbic acid prior to administration did not change the anesthetic effect. Those results indicated that ascorbic acid does not directly reduce pentobarbital. Enzymatic activities and levels of the proteins of some cytochrome P450s that make up a potent detoxification system for pentobarbital showed no changes in the genetically modified mice examined. Thus, ascorbic acid also had no effect on the detoxification system in the liver. The prolonged duration of LORR in the Akr1a-/- mice caused by pentobarbital and the neutralization of the anesthetic effect by ascorbic acid together with other results imply that ascorbic acid alters the responses of the neuronal system to anesthetics. Significance Pentobarbital action is increased under conditions of ascorbic acid deficiency, and this may have to be taken into account when anesthetizing malnourished patients.",
author = "Junitsu Ito and Noriyuki Otsuki and Xuhong Zhang and Tasuku Konno and Toshihiro Kurahashi and Motoko Takahashi and Mayumi Yamato and Yuta Matsuoka and Ken-Ichi Yamada and Satoshi Miyata and Junichi Fujii",
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T1 - Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a-knockout mice

AU - Ito, Junitsu

AU - Otsuki, Noriyuki

AU - Zhang, Xuhong

AU - Konno, Tasuku

AU - Kurahashi, Toshihiro

AU - Takahashi, Motoko

AU - Yamato, Mayumi

AU - Matsuoka, Yuta

AU - Yamada, Ken-Ichi

AU - Miyata, Satoshi

AU - Fujii, Junichi

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N2 - Aims Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, is highly expressed in the liver and is involved in both the detoxification of carbonyl compounds and ascorbic acid biosynthesis. By comparison with wild-type mice, Akr1a-knockout (Akr1a-/-) mice and human Akrla-transgenic (Akr1atg/+) mice experience different anesthetic actions from pentobarbital - prolonged in Akr1a-knockout (Akr1a -/-) mice and shortened in human Akrla-transgenic (Akr1a tg/+) mice. Main methods We investigated this alteration in the anesthetic efficacy of pentobarbital in Akr1a genetically modified mice. Key findings Neither the cytosolic protein of wild-type mouse liver nor purified rat AKR1A directly reduced pentobarbital. Ascorbic acid administration neutralized the prolonged duration of the loss of the righting reflex (LORR) in Akr1a -/- mice, but preincubation of pentobarbital with ascorbic acid prior to administration did not change the anesthetic effect. Those results indicated that ascorbic acid does not directly reduce pentobarbital. Enzymatic activities and levels of the proteins of some cytochrome P450s that make up a potent detoxification system for pentobarbital showed no changes in the genetically modified mice examined. Thus, ascorbic acid also had no effect on the detoxification system in the liver. The prolonged duration of LORR in the Akr1a-/- mice caused by pentobarbital and the neutralization of the anesthetic effect by ascorbic acid together with other results imply that ascorbic acid alters the responses of the neuronal system to anesthetics. Significance Pentobarbital action is increased under conditions of ascorbic acid deficiency, and this may have to be taken into account when anesthetizing malnourished patients.

AB - Aims Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, is highly expressed in the liver and is involved in both the detoxification of carbonyl compounds and ascorbic acid biosynthesis. By comparison with wild-type mice, Akr1a-knockout (Akr1a-/-) mice and human Akrla-transgenic (Akr1atg/+) mice experience different anesthetic actions from pentobarbital - prolonged in Akr1a-knockout (Akr1a -/-) mice and shortened in human Akrla-transgenic (Akr1a tg/+) mice. Main methods We investigated this alteration in the anesthetic efficacy of pentobarbital in Akr1a genetically modified mice. Key findings Neither the cytosolic protein of wild-type mouse liver nor purified rat AKR1A directly reduced pentobarbital. Ascorbic acid administration neutralized the prolonged duration of the loss of the righting reflex (LORR) in Akr1a -/- mice, but preincubation of pentobarbital with ascorbic acid prior to administration did not change the anesthetic effect. Those results indicated that ascorbic acid does not directly reduce pentobarbital. Enzymatic activities and levels of the proteins of some cytochrome P450s that make up a potent detoxification system for pentobarbital showed no changes in the genetically modified mice examined. Thus, ascorbic acid also had no effect on the detoxification system in the liver. The prolonged duration of LORR in the Akr1a-/- mice caused by pentobarbital and the neutralization of the anesthetic effect by ascorbic acid together with other results imply that ascorbic acid alters the responses of the neuronal system to anesthetics. Significance Pentobarbital action is increased under conditions of ascorbic acid deficiency, and this may have to be taken into account when anesthetizing malnourished patients.

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