Hemoglobin vesicles containing methemoglobin and L-tyrosine to suppress methemoglobin formation in vitro and in vivo

Tomoyasu Atoji, Motonari Aihara, Hiromi Sakai, Eishun Tsuchida, Shinji Takeoka

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Hemoglobin (Hb) vesicles have been developed as cellular-type Hb-based O2 carriers in which a purified and concentrated Hb solution is encapsulated with a phospholipid bilayer membrane. Ferrous Hb molecules within an Hb vesicle were converted to ferric metHb by reacting with reactive oxygen species such as hydrogen peroxide (H2O2) generated in the living body or during the autoxidation of oxyHb in the Hb vesicle, and this leads to the loss of O2 binding ability. The prevention of metHb formation by H2O2 in the Hb vesicle is required to prolong the in vivo O2 carrying ability. We found that a mixed solution of metHb and L-tyrosine (L-Tyr) showed an effective H2O2 elimination ability by utilizing the reverse peroxidase activity of metHb with L-Tyr as an electron donor. The time taken for the conversion of half of oxyHb to metHb (T50) was 420 min for the Hb vesicles containing 4 g/dL (620 μM) metHb and 8.5 mM L-Tyr ((metHb/L-Tyr) Hb vesicles), whereas the time of conversion for the conventional Hb vesicles was 25 min by stepwise injection of H2O2 (310 μM) in 10 min intervals. Furthermore, in the (metHb/L-Tyr) Hb vesicles, the metHb percentage did not reach 50% even after 48 h under a pO2 of 40 Torr at 37°C, whereas T50 of the conventional Hb vesicles was 13 h under the same conditions. Moreover, the T50 values of the conventional Hb vesicles and the (metHb/L-Tyr) Hb vesicles were 14 and 44 h, respectively, after injection into rats (20 mL/kg), confirming the remarkable inhibitory effect of metHb formation in vivo in the (metHb/L-Tyr) Hb vesicles.

    Original languageEnglish
    Pages (from-to)1241-1245
    Number of pages5
    JournalBioconjugate Chemistry
    Volume17
    Issue number5
    DOIs
    Publication statusPublished - 2006 Sep

    Fingerprint

    Methemoglobin
    Hemoglobin
    Tyrosine
    Hemoglobins
    In Vitro Techniques
    Injections
    Phospholipids
    Hydrogen peroxide

    ASJC Scopus subject areas

    • Chemistry(all)
    • Organic Chemistry
    • Clinical Biochemistry
    • Biochemistry, Genetics and Molecular Biology(all)
    • Biochemistry

    Cite this

    Hemoglobin vesicles containing methemoglobin and L-tyrosine to suppress methemoglobin formation in vitro and in vivo. / Atoji, Tomoyasu; Aihara, Motonari; Sakai, Hiromi; Tsuchida, Eishun; Takeoka, Shinji.

    In: Bioconjugate Chemistry, Vol. 17, No. 5, 09.2006, p. 1241-1245.

    Research output: Contribution to journalArticle

    Atoji, Tomoyasu ; Aihara, Motonari ; Sakai, Hiromi ; Tsuchida, Eishun ; Takeoka, Shinji. / Hemoglobin vesicles containing methemoglobin and L-tyrosine to suppress methemoglobin formation in vitro and in vivo. In: Bioconjugate Chemistry. 2006 ; Vol. 17, No. 5. pp. 1241-1245.
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    abstract = "Hemoglobin (Hb) vesicles have been developed as cellular-type Hb-based O2 carriers in which a purified and concentrated Hb solution is encapsulated with a phospholipid bilayer membrane. Ferrous Hb molecules within an Hb vesicle were converted to ferric metHb by reacting with reactive oxygen species such as hydrogen peroxide (H2O2) generated in the living body or during the autoxidation of oxyHb in the Hb vesicle, and this leads to the loss of O2 binding ability. The prevention of metHb formation by H2O2 in the Hb vesicle is required to prolong the in vivo O2 carrying ability. We found that a mixed solution of metHb and L-tyrosine (L-Tyr) showed an effective H2O2 elimination ability by utilizing the reverse peroxidase activity of metHb with L-Tyr as an electron donor. The time taken for the conversion of half of oxyHb to metHb (T50) was 420 min for the Hb vesicles containing 4 g/dL (620 μM) metHb and 8.5 mM L-Tyr ((metHb/L-Tyr) Hb vesicles), whereas the time of conversion for the conventional Hb vesicles was 25 min by stepwise injection of H2O2 (310 μM) in 10 min intervals. Furthermore, in the (metHb/L-Tyr) Hb vesicles, the metHb percentage did not reach 50{\%} even after 48 h under a pO2 of 40 Torr at 37°C, whereas T50 of the conventional Hb vesicles was 13 h under the same conditions. Moreover, the T50 values of the conventional Hb vesicles and the (metHb/L-Tyr) Hb vesicles were 14 and 44 h, respectively, after injection into rats (20 mL/kg), confirming the remarkable inhibitory effect of metHb formation in vivo in the (metHb/L-Tyr) Hb vesicles.",
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    T1 - Hemoglobin vesicles containing methemoglobin and L-tyrosine to suppress methemoglobin formation in vitro and in vivo

    AU - Atoji, Tomoyasu

    AU - Aihara, Motonari

    AU - Sakai, Hiromi

    AU - Tsuchida, Eishun

    AU - Takeoka, Shinji

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    AB - Hemoglobin (Hb) vesicles have been developed as cellular-type Hb-based O2 carriers in which a purified and concentrated Hb solution is encapsulated with a phospholipid bilayer membrane. Ferrous Hb molecules within an Hb vesicle were converted to ferric metHb by reacting with reactive oxygen species such as hydrogen peroxide (H2O2) generated in the living body or during the autoxidation of oxyHb in the Hb vesicle, and this leads to the loss of O2 binding ability. The prevention of metHb formation by H2O2 in the Hb vesicle is required to prolong the in vivo O2 carrying ability. We found that a mixed solution of metHb and L-tyrosine (L-Tyr) showed an effective H2O2 elimination ability by utilizing the reverse peroxidase activity of metHb with L-Tyr as an electron donor. The time taken for the conversion of half of oxyHb to metHb (T50) was 420 min for the Hb vesicles containing 4 g/dL (620 μM) metHb and 8.5 mM L-Tyr ((metHb/L-Tyr) Hb vesicles), whereas the time of conversion for the conventional Hb vesicles was 25 min by stepwise injection of H2O2 (310 μM) in 10 min intervals. Furthermore, in the (metHb/L-Tyr) Hb vesicles, the metHb percentage did not reach 50% even after 48 h under a pO2 of 40 Torr at 37°C, whereas T50 of the conventional Hb vesicles was 13 h under the same conditions. Moreover, the T50 values of the conventional Hb vesicles and the (metHb/L-Tyr) Hb vesicles were 14 and 44 h, respectively, after injection into rats (20 mL/kg), confirming the remarkable inhibitory effect of metHb formation in vivo in the (metHb/L-Tyr) Hb vesicles.

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