Alayash Abdu I, D'Agnillo Felice, Buehler Paul W
Center for Biologics Evaluation and Research, Food and Drug Administration, Laboratory of Biochemistry and Vascular Biology, Division of Hematology, National Institutes of Health Campus, Bethesda, MD 20892, USA.
Expert Opin Biol Ther. 2007 May;7(5):665-75. doi: 10.1517/14712598.7.5.665.
Chemically modified or recombinant hemoglobin (Hb)-based oxygen carriers (HBOCs) have been developed as oxygen therapeutics or 'blood substitutes' for use in a variety of clinical settings. Oxidative and nitrosative reactions of acellular Hb can limit the effectiveness and compromise the safety of HBOCs. The reactions between Hb and biologically relevant redox active molecules may also perturb redox sensitive signaling pathways. In recent years, systematic in vitro and in vivo structural and functional evaluation of several HBOCs has been carried out and, in some cases, delineated the 'structural' origin of their toxicity. This enables potential protective strategies against Hb-mediated side reactions to be rationally suggested. Here the authors provide an overview of their research experiences, novel insights into the molecular basis of toxicities of these products and some lessons learned.
化学修饰或重组的基于血红蛋白（Hb）的氧载体（HBOCs）已被开发用作氧治疗剂或“血液替代品”，用于各种临床环境。无细胞Hb的氧化和亚硝化反应会限制HBOCs的有效性并损害其安全性。Hb与生物相关的氧化还原活性分子之间的反应也可能扰乱氧化还原敏感信号通路。近年来，已经对几种HBOCs进行了系统的体外和体内结构与功能评估，并且在某些情况下，阐明了其毒性的“结构”起源。这使得能够合理地提出针对Hb介导的副反应的潜在保护策略。在此，作者概述了他们的研究经验、对这些产品毒性分子基础的新见解以及一些经验教训。
