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学術誌査読

12 被引用数 (Scopus)


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.

ジャーナルLife Sciences
出版ステータス出版済み - 1月 24 2014

!!!All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 薬理学、毒性学および薬学(全般)


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