Everse J, Hsia N
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Free Radic Biol Med. 1997;22(6):1075-99. doi: 10.1016/s0891-5849(96)00499-6.
Recent research on the potential use of hemoglobin derivatives as a blood substitute has revealed that the administration of large quantities of free hemoglobin into the circulation results in a variety of toxic side effects. Because it has been well established that hemoglobin, like myoglobin, has considerable pro-oxidant activity, a number of studies have appeared suggesting that the administered hemoglobins may catalyze various oxidative and peroxidative reactions, which in turn, would cause the observed pathologic conditions. This occurs as a result of the in vivo formation of highly oxidized forms of the native and modified hemoglobins. In addition, it has been proposed that considerable amounts of free hemin and iron may be generated as a result of the catabolism of the injected hemoglobin. Hemin is known to be very toxic when present in large amounts, and iron could catalyze the formation of hydroxyl radicals via Fenton-type reactions. Thus, the toxic activities of catabolic products of hemoglobin could also be involved in all or part of the observed side effects. The purpose of this review is to consider the conditions under which reactive species of hemoglobin may be formed in vivo, their potential reactivity, and whether their individual or combined oxidative activities could account for the biological damage that is observed in vivo following hemoglobin transfusions.
近期关于将血红蛋白衍生物用作血液替代品的潜在用途的研究表明，向循环系统中大量输注游离血红蛋白会导致多种毒性副作用。由于已经充分证实血红蛋白与肌红蛋白一样具有相当强的促氧化活性，因此出现了一些研究表明，输注的血红蛋白可能会催化各种氧化和过氧化反应，进而导致所观察到的病理状况。这是由于体内天然和修饰血红蛋白形成了高度氧化形式的结果。此外，有人提出，注入的血红蛋白分解代谢可能会产生大量游离血红素和铁。已知大量存在时血红素具有很强的毒性，并且铁可通过芬顿型反应催化羟基自由基的形成。因此，血红蛋白分解代谢产物的毒性活性也可能全部或部分参与了所观察到的副作用。本综述的目的是探讨血红蛋白的反应性物种在体内形成的条件、它们的潜在反应性，以及它们各自或联合的氧化活性是否能够解释在输注血红蛋白后体内观察到的生物损伤。
