Premium
Prolonged functional life span of artificial red cells (Hb‐vesicles) by coexistence of an electron mediator in blood stream (794.7)
Author(s) -
Sakai Hiromi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.794.7
Subject(s) - methemoglobin , chemistry , vesicle , hemoglobin , electron transfer , in vivo , autoxidation , liposome , biophysics , pharmacology , biochemistry , biology , membrane , photochemistry , microbiology and biotechnology
Artificial red cells (Hb‐vesicles, HbV) are one candidate of a transfusion alternative. A purified and concentrated Hb solution is compartmentalized in phospholipid vesicles (liposomes) (Sakai et al., JBC 2008;283:1508‐17). The safety and efficacy of HbV have been examined extensively in preclinical studies. Because of the lack of metHb‐reduction system that is originally present in RBC, HbV gradually increases the metHb level through autoxidation after intravenous injection. In this paper we aimed to prolong the functional life span of HbV by reducing ferric metHb (Fe3+) to ferrous state (Fe2+) by co‐injection of a water‐soluble electron mediator (EM+), and find out the mechanism of in vivo metHb reduction system. HbV was injected intravenously ([Hb] = 10 g/dL, 20 mL/kg) to anesthetized male Wistar rats. After the metHb level of HbV reached to 50%, EM+ was injected intravenously. The metHb level rapidly reduced to around 10%. In vitro experiments of mixing HbV with blood (or washed RBC) and EM+ showed metHb reduction, but not with plasma and EM+. These results indicate that RBC is a source of an electron to reduce EM+ to EMH and it moves across the lipid membranes to pass the electron to metHb in HbV. EM+ effectively mediates electron transfer from RBC to HbV in blood circulation. The detailed mechanism of electron transfer will be presented. Grant Funding Source : Grant‐in‐aid for Scientific Research from JSPS