Hemolysis (i.e., red blood cell lysis) can increase circulatory levels of cell-free hemoglobin (Hb) and its degradation by-products, namely heme (h) and iron (Fe). Under homeostasis, minor increases in these three hemolytic by-products (Hb/h/Fe) are rapidly scavenged and cleared by natural plasma proteins. Under certain pathophysiological conditions, scavenging systems become overwhelmed, leading to the accumulation of Hb/h/Fe in the circulation. Unfortunately, these species cause various side effects such as vasoconstriction, hypertension, and oxidative organ damage. Therefore, various therapeutics strategies are in development, ranging from supplementation with depleted plasma scavenger proteins to engineered biomimetic protein constructs capable of scavenging multiple hemolytic species. In this review, we briefly describe hemolysis and the characteristics of the major plasma-derived protein scavengers of Hb/h/Fe. Finally, we present novel engineering approaches designed to address the toxicity of these hemolytic by-products.

中文翻译：

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血红蛋白、血红素和铁解毒的工程治疗方法

溶血（即红细胞裂解）可以增加无细胞血红蛋白 (Hb) 及其降解副产物，即血红素 (h) 和铁 (Fe) 的循环水平。在稳态下，这三种溶血副产物 (Hb/h/Fe) 的少量增加会被天然血浆蛋白迅速清除。在某些病理生理条件下，清除系统不堪重负，导致循环中 Hb/h/Fe 的积累。不幸的是，这些物种会引起各种副作用，例如血管收缩、高血压和氧化器官损伤。因此，各种治疗策略正在开发中，从补充耗尽的血浆清除剂蛋白到能够清除多种溶血物质的工程仿生蛋白构建体。在这篇综述中，我们简要描述了溶血以及主要血浆来源的 Hb/h/Fe 蛋白清除剂的特征。最后，我们提出了旨在解决这些溶血副产物的毒性的新颖工程方法。