Cavalcanti Liara Freitas, Chagas Silva Isabela, do Nascimento Thiago Henrique Daniel, de Melo Jôse, Grion Cintia Magalhães Carvalho, Cecchini Alessandra Lourenço, Cecchini Rubens
Department of General Pathology, Laboratory of Pathophysiology and Free Radicals, State University of Londrina, UEL, Londrina, Brazil.
Department of General Pathology, Laboratory of Molecular Pathology, State University of Londrina, UEL, Londrina, Brazil.
Free Radic Res. 2022 Nov-Dec;56(11-12):740-748. doi: 10.1080/10715762.2023.2174021. Epub 2023 Feb 1.
Oxidative Stress (OS) is involved in the pathogenesis of COVID-19 and in the mechanisms by which SARS-CoV-2 causes injuries to tissues, leading to cytopathic hypoxia and ultimately multiple organ failure. The measurement of blood glutathione (GSH), HO, and catalase activity may help clarify the pathophysiology pathways of this disease. We developed and standardized a sensitive and specific chemiluminescence technique for HO and GSH measurement in plasma and red blood cells of COVID-19 patients admitted to the intensive care unit (ICU). Contrary to what was expected, the plasma concentration of HO was substantially reduced (10-fold) in COVID-19 patients compared to the healthy control group. From the cohort of patients discharged from the hospital and those who were deceased, the former showed a 3.6-fold and the later 16-fold HO reduction compared to the healthy control. There was a 4.4 reduction of HO concentration in the deceased group compared to the discharged group. Interestingly, there was no variation in GSH levels between groups, and reduced catalase activity was found in discharged and deceased patients compared to control. These data represent strong evidence that HO is converted into highly reactive oxygen species (ROS), leading to the worst prognosis and death outcome in COVID-19 patients admitted to ICU. Considering the difference in the levels of HO between the control group and the deceased patients, it is proposed the quantification of plasma HO as a marker of disease progression and the induction of the synthesis of antioxidant enzymes as a strategy to reduce the production of oxidative stress during severe COVID-19.HighlightsHO plasma levels is dramatically reduced in patients who deceased compared to those discharged and to the control group.Plasmatic quantification of HO can be possibly used as a predictor of disease progression.Catalase activity is reduced in COVID-19.GSH levels remain unchanged in COVID-19 compared to the control group.
氧化应激（OS）参与了新冠病毒疾病（COVID-19）的发病机制以及严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对组织造成损伤的机制，导致细胞病变性缺氧并最终引发多器官功能衰竭。血液中谷胱甘肽（GSH）、血红素加氧酶（HO）和过氧化氢酶活性的测定可能有助于阐明该疾病的病理生理途径。我们开发并标准化了一种灵敏且特异的化学发光技术，用于测量入住重症监护病房（ICU）的COVID-19患者血浆和红细胞中的HO和GSH。与预期相反，COVID-19患者血浆中HO的浓度与健康对照组相比大幅降低（10倍）。在出院患者和死亡患者队列中，与健康对照组相比，前者HO降低了3.6倍，后者降低了16倍。与出院组相比，死亡组的HO浓度降低了4.4倍。有趣的是，各组之间GSH水平没有变化，并且与对照组相比，出院患者和死亡患者的过氧化氢酶活性降低。这些数据有力地证明，HO转化为高活性氧物种（ROS），导致入住ICU的COVID-19患者预后更差和死亡结局。考虑到对照组和死亡患者之间HO水平的差异，建议将血浆HO的定量作为疾病进展的标志物，并诱导抗氧化酶的合成作为减少重症COVID-19期间氧化应激产生的策略。
重点
与出院患者和对照组相比，死亡患者的血浆HO水平显著降低。
血浆HO的定量可能用作疾病进展的预测指标。
COVID-19患者的过氧化氢酶活性降低。
与对照组相比，COVID-19患者的GSH水平保持不变。
