Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute

Risa Haruki; Takuya Kimura; Hitomi Iwasaki; Kana Yamada; Ikuo Kamiyama; Mitsutomo Kohno; Kazuaki Taguchi; Saori Nagao; Toru Maruyama; Masaki Otagiri; Teruyuki Komatsu

doi:10.1038/srep12778

Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute

Risa Haruki, Takuya Kimura, Hitomi Iwasaki, Kana Yamada, Ikuo Kamiyama, Mitsutomo Kohno, Kazuaki Taguchi, Saori Nagao, Toru Maruyama, Masaki Otagiri, Teruyuki Komatsu

Department of Surgery

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell structured hemoglobin-albumin cluster designated as "HemoAct", is an O 2 -carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125 I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.

Original language	English
Article number	12778
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep12778
Publication status	Published - 2015 Jul 29

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title = "Safety Evaluation of Hemoglobin-Albumin Cluster {"}HemoAct{"} as a Red Blood Cell Substitute",

abstract = "A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell structured hemoglobin-albumin cluster designated as {"}HemoAct{"}, is an O 2 -carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125 I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.",

author = "Risa Haruki and Takuya Kimura and Hitomi Iwasaki and Kana Yamada and Ikuo Kamiyama and Mitsutomo Kohno and Kazuaki Taguchi and Saori Nagao and Toru Maruyama and Masaki Otagiri and Teruyuki Komatsu",

note = "Funding Information: This work was supported by a Grant-in-Aid for Scientific Research on Innovative Area (“Coordination Programming” Area 2107, No. 21108013) from MEXT Japan, and by a Joint Research Grant from the Institute of Science and Engineering, Chuo University. The authors acknowledge Mr. Katsunori Maejima, Chuo University, for skillful experiments related to Hb purification, Dr. Keitaro Sou, Waseda University, for his kind support on viscosity measurements, Dr. Yuichiro Hayashi, Keio University, for valuable comments related to histopathologic observations, and the members of the Radioisotope Center, Kumamoto University, for important contributions to pharmacokinetic experiments.",

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AU - Haruki, Risa

AU - Kimura, Takuya

AU - Iwasaki, Hitomi

AU - Yamada, Kana

AU - Kamiyama, Ikuo

AU - Kohno, Mitsutomo

AU - Taguchi, Kazuaki

AU - Nagao, Saori

AU - Maruyama, Toru

AU - Otagiri, Masaki

AU - Komatsu, Teruyuki

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PY - 2015/7/29

Y1 - 2015/7/29

N2 - A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell structured hemoglobin-albumin cluster designated as "HemoAct", is an O 2 -carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125 I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.

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Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute

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