Physiological capacity of the reticuloendothelial system for the degradation of hemoglobin vesicles (artificial oxygen carriers) after massive intravenous doses by daily repeated infusions for 14 days

Hiromi Sakai, Yohei Masada, Hirohisa Horinouchi, Eiji Ikeda, Keitaro Sou, Shinji Takeoka, Makoto Suematsu, Masuhiko Takaori, Koichi Kobayashi, Eishun Tsuchida

研究成果: Article査読

54 被引用数 (Scopus)

抄録

A hemoglobin vesicle (HbV; diameter 252 ± 53 nm) or liposome-encapsulated Hb is an artificial oxygen carrier developed for use as a transfusion alternative, and its oxygen-transporting capacity has been well characterized, although critical physiological compartments for the Hb degradation after a massive infusion of HbV and the safety outcome remain unknown. In this study, we aimed to examine the compartments for its degradation by daily repeated infusions (DRI) of HbV, focusing on its influence on the reticuloendothelial system (RES). Male Wistar rats intravenously received the HbV suspension at 10 ml/kg/day for 14 consecutive days. The cumulative infusion volume (140 mi/kg) was equal to 2.5 times the whole blood volume (56 mi/kg). The animals tolerated the DRI well and survived, and body weights continuously increased. One day after DRI, hepatosplenomegaly occurred significantly through the accumulation of large amounts of HbV. Plasma clinical chemistry was overall normal, except for a transient elevation of lipid components derived from HbV. These symptoms subsided 14 days after DRI. Hemosiderin deposition and up-regulation of heme oxygenase-1 coincided in the liver and spleen but were not evident in the parenchyma of these organs. Furthermore, the plasma iron and bilirubin levels remained unchanged, suggesting that the heme-degrading capacity of the RES did not surpass the ability to eliminate bilirubin. In conclusion, phospholipid vesicles for the encapsulation of Hb would be beneficial for heme detoxification through their preferential delivery to the RES, a physiological compartment for degradation of senescent RBCs, even at doses greater than putative clinical doses.

本文言語English
ページ(範囲)874-884
ページ数11
ジャーナルJournal of Pharmacology and Experimental Therapeutics
311
3
DOI
出版ステータスPublished - 2004 12

ASJC Scopus subject areas

  • 分子医療
  • 薬理学

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