Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy

Toshihiro Kurahashi, Jaeyong Lee, Atsunori Nabeshima, Takujiro Homma, Eun Sil Kang, Yuka Saito, Sohsuke Yamada, Toshiyuki Nakayama, Ken-Ichi Yamada, Satoshi Miyata, Junichi Fujii

研究成果: ジャーナルへの寄稿記事

14 引用 (Scopus)

抄録

Aldehyde reductase (AKR1A) plays a role in the biosynthesis of ascorbic acid (AsA), and AKR1A-deficient mice produce about 10-15% of the AsA that is produced by wild-type mice. We found that acetaminophen (AAP) hepatotoxicity was aggravated in AKR1A-deficient mice. The pre-administration of AsA in the drinking water markedly ameliorated the AAP hepatotoxicity in the AKR1A-deficient mice. Treatment of the mice with AAP decreased both glutathione and AsA levels in the liver in the early phase after AAP administration, and an AsA deficiency delayed the recovery of the glutathione content in the healing phase. While in cysteine supply systems; a neutral amino acid transporter ASCT1, a cystine transporter xCT, enzymes for the transsulfuration pathway, and autophagy markers, were all elevated in the liver as the result of the AAP treatment, the AsA deficiency suppressed their induction. Thus, AsA appeared to exert a protective effect against AAP hepatotoxicity by ameliorating the supply of cysteine that is available for glutathione synthesis as a whole. Because some drugs produce reactive oxygen species, resulting in the consumption of glutathione during the metabolic process, the intake of sufficient amounts of AsA would be beneficial for protecting against the hepatic damage caused by such drugs.

元の言語英語
ページ(範囲)36-46
ページ数11
ジャーナルArchives of Biochemistry and Biophysics
604
DOI
出版物ステータス出版済み - 8 15 2016

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Autophagy
Acetaminophen
Ascorbic Acid
Glutathione
Recovery
Ascorbic Acid Deficiency
Cysteine
Liver
Neutral Amino Acid Transport Systems
Aldehyde Reductase
Cystine
Drinking Water
Pharmaceutical Preparations
Reactive Oxygen Species
Biosynthesis
Enzymes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

これを引用

Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy. / Kurahashi, Toshihiro; Lee, Jaeyong; Nabeshima, Atsunori; Homma, Takujiro; Kang, Eun Sil; Saito, Yuka; Yamada, Sohsuke; Nakayama, Toshiyuki; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi.

:: Archives of Biochemistry and Biophysics, 巻 604, 15.08.2016, p. 36-46.

研究成果: ジャーナルへの寄稿記事

Kurahashi, T, Lee, J, Nabeshima, A, Homma, T, Kang, ES, Saito, Y, Yamada, S, Nakayama, T, Yamada, K-I, Miyata, S & Fujii, J 2016, 'Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy', Archives of Biochemistry and Biophysics, 巻. 604, pp. 36-46. https://doi.org/10.1016/j.abb.2016.06.004
Kurahashi, Toshihiro ; Lee, Jaeyong ; Nabeshima, Atsunori ; Homma, Takujiro ; Kang, Eun Sil ; Saito, Yuka ; Yamada, Sohsuke ; Nakayama, Toshiyuki ; Yamada, Ken-Ichi ; Miyata, Satoshi ; Fujii, Junichi. / Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy. :: Archives of Biochemistry and Biophysics. 2016 ; 巻 604. pp. 36-46.
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abstract = "Aldehyde reductase (AKR1A) plays a role in the biosynthesis of ascorbic acid (AsA), and AKR1A-deficient mice produce about 10-15{\%} of the AsA that is produced by wild-type mice. We found that acetaminophen (AAP) hepatotoxicity was aggravated in AKR1A-deficient mice. The pre-administration of AsA in the drinking water markedly ameliorated the AAP hepatotoxicity in the AKR1A-deficient mice. Treatment of the mice with AAP decreased both glutathione and AsA levels in the liver in the early phase after AAP administration, and an AsA deficiency delayed the recovery of the glutathione content in the healing phase. While in cysteine supply systems; a neutral amino acid transporter ASCT1, a cystine transporter xCT, enzymes for the transsulfuration pathway, and autophagy markers, were all elevated in the liver as the result of the AAP treatment, the AsA deficiency suppressed their induction. Thus, AsA appeared to exert a protective effect against AAP hepatotoxicity by ameliorating the supply of cysteine that is available for glutathione synthesis as a whole. Because some drugs produce reactive oxygen species, resulting in the consumption of glutathione during the metabolic process, the intake of sufficient amounts of AsA would be beneficial for protecting against the hepatic damage caused by such drugs.",
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AU - Kang, Eun Sil

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