Hemoglobin-based oxygen carriers: from mechanisms of toxicity and clearance to rational drug design

被引：111

作者：

Buehler, Paul W. ^{[2
]}

D'Agnillo, Felice ^{[2
]}

Schaer, Dominik J. ^{[1
]}

机构：

[1] Univ Zurich, Zurich, Switzerland

[2] US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD 20014 USA

来源：

TRENDS IN MOLECULAR MEDICINE | 2010年 / 16卷 / 10期

基金：

瑞士国家科学基金会;

关键词：

CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; INDUCED RENAL-FAILURE; NITRIC-OXIDE; SCAVENGER RECEPTOR; BLOOD SUBSTITUTES; ENDOTHELIAL-CELLS; HEME OXYGENASE-1; BACTERIAL-ENDOTOXIN; ELECTRON-MICROSCOPY;

D O I：

10.1016/j.molmed.2010.07.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hemoglobin-based oxygen carriers (HBOCs) have been developed to support blood oxygen transport capacity during hemorrhagic shock, hemolysis and ischemic insult. Existing product candidates have demonstrated considerable efficacy in experimental animal models and in clinical trial subjects; however, severe adverse safety signals that appeared in recent phase II and phase Ill clinical trials involving certain HBOCs have in part hindered further development and licensing. Emerging insights into hemoglobin (Hb) toxicity as well as physiologic Hb scavengers such as haptoglobin and CD163 that are capable of detoxifying extracellular Hb in vivo suggest that alternative product candidates could be designed. Together with novel animal models and biomarkers tailored to monitor the effects of extracellular Hb, a new generation of HBOCs can be envisioned.

引用

页码：447 / 457

页数：11

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