Metabolism of hemoglobin-vesicles (artificial oxygen carriers) and their influence on organ functions in a rat model.
Phospholipid vesicles encapsulating Hb (Hb-vesicles: HbV) have been developed for use as artificial O(2) carriers (250 nm phi). As one of the safety evaluations, we analyzed the influence of HbV on the organ functions by laboratory tests of plasma on a total of 29 analytes. The HbV suspension ([Hb]=10 g/dl) was intravenously infused into male Wistar rats (20 ml/kg; whole blood = 56 ml/kg). The blood was withdrawn at 8h, and 1, 2, 3, and 7 days after infusion, and the plasma was ultracentrifuged to remove HbV in order to avoid its interference effect on the analytes. Enzyme concentrations, AST, ALT, ALP, and LAP showed significant, but minor changes, and did not show a sign of a deteriorative damage to the liver that was one of the main organs for the HbV entrapment and the succeeding metabolism. The amylase and lipase activities showed reversible changes, however, there was no morphological changes in pancreas. Plasma bilirubin and iron did not increase in spite of the fact that a large amount of Hb was metabolized in the macrophages. Cholesterols, phospholipids, and beta-lipoprotein transiently increased showing the maximum at 1 or 2 days, and returned to the control level at 7 days. They should be derived from the membrane components of HbV that are liberated from macrophages entrapping HbV. Together with the previous report of the prompt metabolism of HbV in the reticuloendothelial system by histopathological examination, it can be concluded that HbV infusion transiently modified the values of the analytes without any irreversible damage to the corresponding organs at the bolus infusion rate of 20 ml/kg.
Sakai
Hiromi
H
Advanced Research Institute for Science and Engineering, Waseda University, Okubo 3-4-1, Shinjukuku, Tokyo 169-8555, Japan.
Horinouchi
Hirohisa
H
Masada
Yohei
Y
Takeoka
Shinji
S
Ikeda
Eiji
E
Takaori
Masuhiko
M
Kobayashi
Koichi
K
Tsuchida
Eishun
E
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006454:Hemoglobins / Q000008:administration & dosage* / Q000737:chemistry; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010100:Oxygen / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001802:Blood Substitutes; D004337:Drug Carriers; D006454:Hemoglobins; D008081:Liposomes; D010100:Oxygen