Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model

Maiko Kaga, Heng Li, Hidenobu Ohta, Kazuaki Taguchi, Shigeru Ogaki, Hitomi Izumi, Masumi Inagaki, Shigeru Tsuchiya, Kunihiro Okamura, Masaki Otagiri, Hiromi Sakai, Nobuo Yaegashi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aims: Liposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250 nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy. Main methods: Pregnant rats intravenously received HbV bolus injections at 2 ml/kg/day for the last 7 consecutive days till term. The cumulative infusion volume (14 ml/kg) was equal to 25% of the whole blood volume (56 ml/kg). Key findings: Maternal DRI of HbV had no obvious side effects on the pregnant mother or on fetal development. Maternal vital signs, plasma clinical chemistry, and blood gas parameters were overall normal after DRI of HbV. In addition, maternal/fetal transfer of HbV was limited to the placenta and HbV did not reach the fetus. Histopathological examination with human hemoglobin antibody detected HbV accumulation in the maternal spleen, liver, kidney, and placenta, but not in the fetuses. These results were also confirmed by a pharmacokinetic study using 125I-labeled HbV. Significance: This safety study of HbV use in the pregnant mother and fetus will contribute to a possible application of HbV as a potential treatment for fetal hypoxia by supplying oxygen through the placenta.

Original languageEnglish
Pages (from-to)420-428
Number of pages9
JournalLife Sciences
Volume91
Issue number11-12
DOIs
Publication statusPublished - 2012 Oct 5
Externally publishedYes

Fingerprint

Liposomes
Rats
Hemoglobins
Fetus
Mothers
Placenta
Pregnancy
Clinical Chemistry
Fetal Development
Blood
Fetal Hypoxia
Oxygen
Plasmas
Safety
Mononuclear Phagocyte System
Pharmacokinetics
Vital Signs
Blood Volume
Liver
Rodentia

Keywords

  • Development
  • Hemoglobin vesicles
  • Mother-fetus transfer
  • Placenta
  • Pregnancy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model. / Kaga, Maiko; Li, Heng; Ohta, Hidenobu; Taguchi, Kazuaki; Ogaki, Shigeru; Izumi, Hitomi; Inagaki, Masumi; Tsuchiya, Shigeru; Okamura, Kunihiro; Otagiri, Masaki; Sakai, Hiromi; Yaegashi, Nobuo.

In: Life Sciences, Vol. 91, No. 11-12, 05.10.2012, p. 420-428.

Research output: Contribution to journalArticle

Kaga, M, Li, H, Ohta, H, Taguchi, K, Ogaki, S, Izumi, H, Inagaki, M, Tsuchiya, S, Okamura, K, Otagiri, M, Sakai, H & Yaegashi, N 2012, 'Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model', Life Sciences, vol. 91, no. 11-12, pp. 420-428. https://doi.org/10.1016/j.lfs.2012.08.021
Kaga, Maiko ; Li, Heng ; Ohta, Hidenobu ; Taguchi, Kazuaki ; Ogaki, Shigeru ; Izumi, Hitomi ; Inagaki, Masumi ; Tsuchiya, Shigeru ; Okamura, Kunihiro ; Otagiri, Masaki ; Sakai, Hiromi ; Yaegashi, Nobuo. / Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model. In: Life Sciences. 2012 ; Vol. 91, No. 11-12. pp. 420-428.
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AU - Kaga, Maiko

AU - Li, Heng

AU - Ohta, Hidenobu

AU - Taguchi, Kazuaki

AU - Ogaki, Shigeru

AU - Izumi, Hitomi

AU - Inagaki, Masumi

AU - Tsuchiya, Shigeru

AU - Okamura, Kunihiro

AU - Otagiri, Masaki

AU - Sakai, Hiromi

AU - Yaegashi, Nobuo

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N2 - Aims: Liposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250 nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy. Main methods: Pregnant rats intravenously received HbV bolus injections at 2 ml/kg/day for the last 7 consecutive days till term. The cumulative infusion volume (14 ml/kg) was equal to 25% of the whole blood volume (56 ml/kg). Key findings: Maternal DRI of HbV had no obvious side effects on the pregnant mother or on fetal development. Maternal vital signs, plasma clinical chemistry, and blood gas parameters were overall normal after DRI of HbV. In addition, maternal/fetal transfer of HbV was limited to the placenta and HbV did not reach the fetus. Histopathological examination with human hemoglobin antibody detected HbV accumulation in the maternal spleen, liver, kidney, and placenta, but not in the fetuses. These results were also confirmed by a pharmacokinetic study using 125I-labeled HbV. Significance: This safety study of HbV use in the pregnant mother and fetus will contribute to a possible application of HbV as a potential treatment for fetal hypoxia by supplying oxygen through the placenta.

AB - Aims: Liposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250 nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy. Main methods: Pregnant rats intravenously received HbV bolus injections at 2 ml/kg/day for the last 7 consecutive days till term. The cumulative infusion volume (14 ml/kg) was equal to 25% of the whole blood volume (56 ml/kg). Key findings: Maternal DRI of HbV had no obvious side effects on the pregnant mother or on fetal development. Maternal vital signs, plasma clinical chemistry, and blood gas parameters were overall normal after DRI of HbV. In addition, maternal/fetal transfer of HbV was limited to the placenta and HbV did not reach the fetus. Histopathological examination with human hemoglobin antibody detected HbV accumulation in the maternal spleen, liver, kidney, and placenta, but not in the fetuses. These results were also confirmed by a pharmacokinetic study using 125I-labeled HbV. Significance: This safety study of HbV use in the pregnant mother and fetus will contribute to a possible application of HbV as a potential treatment for fetal hypoxia by supplying oxygen through the placenta.

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