SEPARATION AND CHARACTERIZATION OF ALTERED HEME PRODUCTS

血红蛋白血液代用品毒性的一种潜在机制 涉及血红蛋白与形成的氧代谢产物的反应 缺血组织的再灌注。 这可能会导致一种有害的途径 其中氧化损伤的血红蛋白释放其血红素，随后， 有毒的铁 我们测试了一些化学物质的敏感性， 修饰血红蛋白对过氧化氢氧化损伤的保护作用 （H2O2）。 用低水平的H2O2处理血红蛋白产生可溶性 随后使用HPLC分离蛋白结合的血红素产物。 在α亚基处交联的人血红蛋白显示出典型的 比其他形式的血红蛋白更倾向于氧化修饰 修改. H_2O_2与H_2O_2反应生成的血红素加合物 血红蛋白在NADPH黄递酶中几乎没有或没有氧化酶活性 高铁血红蛋白还原酶系统 目前也在采取类似的做法 评估其他基于血红蛋白的红细胞替代品的敏感性 以确定血红素的分子基础， 蛋白质改变 血红蛋白氧化损伤的可能性 解决方案打开了一个关键的研究领域， 在任何本代血红蛋白产品将 作为再灌注剂是成功的。

One potential mechanism of toxicity of hemoglobin-based blood substitutes involves the reaction of hemoglobin with oxygen metabolites formed upon reperfusion of ischemic tissues. This could lead to a deleterious pathway in which oxidatively damaged hemoglobin releases its heme and subsequently, its toxic iron. We tested the susceptibility of a number of chemically modified hemoglobins to oxidative damage caused by hydrogen peroxide (H2O2). Treatment of hemoglobins with low levels of H2O2 produced soluble protein-bound heme products that were subsequently isolated using HPLC. Human hemoglobin cross-linked at the alpha subunits showed a typical propensity to oxidative modification than other forms of hemoglobin modifications. The heme derived adducts from the reaction of H2O2 with hemoglobins showed little or no oxidase activity in the NADPH-diaphorase methemoglobin reductase system. A similar approach is currently underway to assess the susceptibility of other hemoglobin-based red cell substitutes to oxidative damage in order to determine the molecular basis of heme and protein alterations. The potential for oxidative damage by hemoglobin solutions opens a critical field of study that will have to be well understood before any of the present generation of hemoglobin products will be successful as a reperfusion agent.