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Intrahepatic Delivery of Glutathione by Conjugation to Dextran

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Abstract

Glutathione was covalently attached to dextran (T-40) by the CNBr activation method. The compound obtained was a water-soluble powder containing 10 (w/w%) glutathione, which was gradually released from the conjugate in aqueous media. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of γ-glutamylcysteine synthetase, exhibited a significant increase in hepatic glutathione level after intravenous injection of the conjugate. In mice given a lethal dose of acetaminophen, the survival rate increased progressively with coadministration of the conjugate, whereas little improvement was found when free glutathione was given. The conjugate maintained the serum transaminase activities at lower level after acetaminophen administration. These findings suggest that the dextran conjugate of glutathione is transported into hepatic cells and is intracellulary hydrolyzed to free form, which protects mice from hepatotoxicity due to acetaminophen.

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Authors and Affiliations

  1. Department of Pharmacy and Pharmaceutical Sciences, Fuku-yama University, Fukuyama, Hiroshima, 729-02, Japan

    Yoshiharu Kaneo

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  1. Yoshiharu Kaneo
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  2. Yumie Fujihara
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  3. Tetsuro Tanaka
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  4. Yoko Kozawa
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  5. Hideki Mori
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  6. Sadao Iguchi
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Kaneo, Y., Fujihara, Y., Tanaka, T. et al. Intrahepatic Delivery of Glutathione by Conjugation to Dextran. Pharm Res 6, 1025–1031 (1989). https://doi.org/10.1023/A:1015922303051

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