Hershko C, Weatherall D J
Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.
Crit Rev Clin Lab Sci. 1988;26(4):303-45. doi: 10.3109/10408368809105894.
Because of the catalytic action of iron in one-electron redox reactions, it has a key role in the formation of harmful oxygen derivatives and production of peroxidative damage to vital cellular structures. The clinical manifestations of iron overload may be prevented and even reversed by the effective administration of the iron-chelating drug deferoxamine (DF). Recent experimental evidence suggests that DF may also be useful in modifying disease conditions unrelated to iron overload by preventing the formation of free radicals, the powerful final effectors of tissue damage resulting from the respiratory burst of granulocytes and macrophages participating in the inflammatory response. Although much experimental work is still needed, this novel approach in iron-chelating therapy may have far-reaching implications in the management of autoimmune disease, adult respiratory distress syndrome, and organ transplantation. The poor intestinal absorption of DF, its almost prohibitive price, and short duration of action underline the need for new, orally effective iron chelators. A number of very promising orally effective drugs have been identified in recent years, such as the polyanionic amines, aryl hydrazones, and hydroxypyridones. Further development for clinical use of this new generation of iron-chelating drugs is a major challenge for future research.
由于铁在单电子氧化还原反应中的催化作用,它在有害氧衍生物的形成以及对重要细胞结构的过氧化损伤产生中起着关键作用。通过有效给予铁螯合剂去铁胺(DF),可预防甚至逆转铁过载的临床表现。最近的实验证据表明,DF还可能通过防止自由基的形成来改善与铁过载无关的疾病状况,自由基是参与炎症反应的粒细胞和巨噬细胞呼吸爆发导致组织损伤的强大最终效应物。尽管仍需要大量实验工作,但这种铁螯合疗法的新方法可能对自身免疫性疾病、成人呼吸窘迫综合征和器官移植的管理具有深远意义。DF肠道吸收差、价格几乎令人望而却步且作用持续时间短,这突出了对新型口服有效铁螯合剂的需求。近年来已鉴定出一些非常有前景的口服有效药物,如聚阴离子胺、芳基腙和羟基吡啶酮。将这新一代铁螯合药物开发用于临床是未来研究的一项重大挑战。