The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators.
The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators.
复制标题
DOI：
10.1016/j.biopha.2021.111228
复制
发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Ibrahim WH
中科院分区：
文献类型：
--
作者：
Habib HM;Ibrahim S;Zaim A;Ibrahim WH
铁超负荷越来越多地被认为是COVID-19发病机制的一个因素。事实上，COVID-19的几种表现，如炎症、高凝状态、高铁蛋白血症和免疫功能障碍，也让人联想到铁过载。虽然铁对所有活细胞都是必需的，但由于铁调节异常和过载而产生的游离未结合铁由于其在活性氧（ROS）的产生中的作用而具有很强的反应性和潜在毒性。ROS与细胞脂质、核酸和蛋白质反应并损伤细胞脂质、核酸和蛋白质，从而激活涉及多种临床病症的急性或慢性炎症过程。此外，铁催化的脂质损伤对新发现的非凋亡性细胞死亡（称为铁凋亡）产生直接的致病作用。与细胞凋亡不同，铁凋亡是免疫原性的，不仅导致细胞死亡扩大，而且还促进一系列与炎症相关的反应。铁螯合剂通常是安全的，并被证明可以保护以铁过载为特征的临床病症中的患者。也有大量证据表明铁螯合剂具有抗病毒活性。此外，天然存在的铁螯合剂乳铁蛋白（Lf）发挥免疫调节以及抗炎作用，并可以结合冠状病毒使用的几种受体，从而阻止它们进入宿主细胞。因此，铁螯合剂在当前COVID-19大流行期间可能具有很高的治疗价值。
Iron overload is increasingly implicated as a contributor to the pathogenesis of COVID-19. Indeed, several of the manifestations of COVID-19, such as inflammation, hypercoagulation, hyperferritinemia, and immune dysfunction are also reminiscent of iron overload. Although iron is essential for all living cells, free unbound iron, resulting from iron dysregulation and overload, is very reactive and potentially toxic due to its role in the generation of reactive oxygen species (ROS). ROS react with and damage cellular lipids, nucleic acids, and proteins, with consequent activation of either acute or chronic inflammatory processes implicated in multiple clinical conditions. Moreover, iron-catalyzed lipid damage exerts a direct causative effect on the newly discovered nonapoptotic cell death known as ferroptosis. Unlike apoptosis, ferroptosis is immunogenic and not only leads to amplified cell death but also promotes a series of reactions associated with inflammation. Iron chelators are generally safe and are proven to protect patients in clinical conditions characterized by iron overload. There is also an abundance of evidence that iron chelators possess antiviral activities. Furthermore, the naturally occurring iron chelator lactoferrin (Lf) exerts immunomodulatory as well as anti-inflammatory effects and can bind to several receptors used by coronaviruses thereby blocking their entry into host cells. Iron chelators may consequently be of high therapeutic value during the present COVID-19 pandemic.
登录
查看更多内容
影响因子：
4.4
作者：
Colafrancesco, S.;Priori, R.;Valesini, G.
通讯作者：
Valesini, G.
影响因子：
8.4
作者：
Edeas, Marvin;Saleh, Jumana;Peyssonnaux, Carole
通讯作者：
Peyssonnaux, Carole
影响因子：
2.8
作者：
Chalmers AW;Shammo JM
通讯作者：
Shammo JM
影响因子：
20.3
作者：
Cohen, Lyora A.;Gutierrez, Lucia;Meyron-Holtz, Esther G.
通讯作者：
Meyron-Holtz, Esther G.
影响因子：
4.4
作者：
De la Rosa, Gonzalo;Yang, De;Oppenheim, Joost J.
通讯作者：
Oppenheim, Joost J.