Naidu Sreus A G, Clemens Roger A, Naidu A Satyanarayan
N-terminus Research Laboratory, Yorba Linda, CA, USA.
Department of International Regulatory Science, University of Southern California School of Pharmacy, Los Angeles, CA, USA.
J Diet Suppl. 2023;20(2):312-371. doi: 10.1080/19390211.2022.2075072. Epub 2022 May 22.
Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. - correlates with reduced O transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). results from an increased iron overload, which triggers a fulminant proinflammatory response - the acute cytokine release syndrome (CRS). Elevated cytokine levels (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 patients is consequential to erythrocyte dysfunction with heme release, increased prothrombin time and elevated D-dimers, cumulatively linked to severe coagulopathies with life-threatening outcomes such as ARDS, and multi-organ failure. Taken together, Fe-R-H dysregulation is implicated in every symptomatic phase of COVID-19. Fe-R-H regulators such as lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, reduce oxidative stress, and improve host defense by optimizing iron metabolism. Due to its pivotal role in 'cytokine storm', ferroptosis is a potential intervention target. Ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, quercetin, and melatonin could prevent mitochondrial lipid peroxidation, up-regulate antioxidant/GSH levels and abrogate iron overload-induced apoptosis through activation of Nrf2 and HO-1 signaling pathways. Iron chelators such as heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid could protect against ferroptosis and restore mitochondrial function, iron-redox potential, and rebalance Fe-R-H status. Therefore, Fe-R-H restoration is a host biomarker-driven potential combat strategy for an effective clinical and post-recovery management of COVID-19.
新型冠状病毒2感染患者中铁代谢的严重失衡在新冠肺炎的每个有症状（轻度、中度至重度）临床阶段都很突出。 - 与红细胞氧运输减少、低氧诱导因子-1α（HIF-1α）过表达、线粒体生物能量学改变以及宿主代谢重编程（HMR）相关。 由铁过载增加引起，铁过载会引发暴发性促炎反应 - 急性细胞因子释放综合征（CRS）。新冠肺炎患者中细胞因子水平升高（如白细胞介素6、肿瘤坏死因子α和C反应蛋白）与铁蛋白/转铁蛋白（TF）比值改变密切相关，这是由于红细胞功能障碍伴血红素释放、凝血酶原时间延长和D-二聚体升高所致，这些因素累积起来与严重凝血病相关，可导致危及生命的后果，如急性呼吸窘迫综合征（ARDS）和多器官功能衰竭。综上所述，铁-红细胞-血红素（Fe-R-H）失调与新冠肺炎的每个有症状阶段都有关。乳铁蛋白（LF）、血红素加氧酶-1（HO-1）、促红细胞生成素（EPO）和铁调素调节剂等Fe-R-H调节剂是天然的生物补充剂，可螯合铁、中和铁介导的自由基、减少氧化应激，并通过优化铁代谢来改善宿主防御。由于铁死亡在“细胞因子风暴”中起关键作用，因此它是一个潜在的干预靶点。铁死亡抑制剂如铁抑素-1、脂氧素他汀-1、槲皮素和褪黑素可以防止线粒体脂质过氧化，上调抗氧化剂/谷胱甘肽（GSH）水平，并通过激活核因子E2相关因子2（Nrf2）和HO-1信号通路消除铁过载诱导的细胞凋亡。肝素、去铁胺、咖啡酸、姜黄素、α-硫辛酸和植酸等铁螯合剂可以预防铁死亡并恢复线粒体功能、铁氧化还原电位，并重平衡Fe-R-H状态。因此，恢复Fe-R-H是一种以宿主生物标志物为驱动的潜在对抗策略，用于新冠肺炎的有效临床和康复后管理。
