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


Buehler, P W; D'Agnillo, F; Schaer, D J (2010). Hemoglobin-based oxygen carriers: from mechanisms of toxicity and clearance to rational drug design. Trends in Molecular Medicine, 16(10):447-457.

Abstract

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 III 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.

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 III 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
Dewey Decimal Classification:610 Medicine & health
Date:2010
Deposited On:01 Feb 2011 16:20
Last Modified:05 Apr 2016 14:41
Publisher:Elsevier
ISSN:1471-4914
Publisher DOI:10.1016/j.molmed.2010.07.006
PubMed ID:20708968
Permanent URL: http://doi.org/10.5167/uzh-44234

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