28. Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins

  1. Andrea Mozzarelli2,3 and
  2. Stefano Bettati2,3
  1. Paul W. Buehler and
  2. Felice D'Agnillo

Published Online: 4 JUL 2011

DOI: 10.1002/9781119975427.ch28

Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood

Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood

How to Cite

Buehler, P. W. and D'Agnillo, F. (2011) Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins, in Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood (eds A. Mozzarelli and S. Bettati), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9781119975427.ch28

Editor Information

  1. 2

    Department of Biochemistry and Molecular Biology, University of Parma, Parma, Italy

  2. 3

    National Institute of Biostructures and Biosystems, Rome, Italy

Author Information

  1. Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), MD, USA

Publication History

  1. Published Online: 4 JUL 2011
  2. Published Print: 12 AUG 2011

ISBN Information

Print ISBN: 9780470686683

Online ISBN: 9781119975427

SEARCH

Keywords:

  • animal models and oxidative biomarkers - preclinical safety of extracellular hemoglobins;
  • hemoglobin-based oxygen carriers (HBOCs) - challenges, linking predictive safety from GLP;
  • primary toxicities of Hbs/HBOCs - standard toxicology/safety pharmacology studies;
  • HBOC safety and efficacy - proposed mechanisms of toxicity;
  • HBOCs, problematic - systemic and pulmonary hypertension;
  • HBOCs, challenging paradigm - standard safety pharmacology and toxicology testing;
  • proof-of-concept models, HBOCs nonclinical evaluation - effects on tissue blood flow;
  • sepsis and/or endotoxemia - overproduction of ROS/reactive nitrogen species (RNS);
  • experimental oxidative biomarkers and extracellular Hb exposure - and heme iron oxidation;
  • markers of in vivo oxidative stress and tissue damage

Summary

This chapter contains sections titled:

  • Disclaimer

  • Introduction

  • HBOC Safety and Efficacy

  • Experimental Oxidative Biomarkers and Extracellular Hb Exposure

  • Markers of in vivo Oxidative Stress and Tissue Damage

  • Conclusion

  • References