Differential redox state and iron regulation in chronic obstructive pulmonary disease, acute respiratory distress syndrome and coronavirus disease 2019

Lorena Duca, Sara Ottolenghi, Silvia Coppola, Rocco Rinaldo, Michele Dei Cas, Federico Maria Rubino, Rita Paroni, Michele Samaja, Davide Alberto Chiumello, Irene Motta

Research output: Contribution to journalArticlepeer-review

Abstract

In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia. To this purpose, we evaluated a panel of redox state biomarkers that may integrate the routine iron metabolism assays to monitor the patients’ inflammatory and oxidative state. We measured redox and hematopoietic regulators in 20 ARDS patients, 20 ambulatory COPD patients, 9 COVID-19 ARDS-like patients, and 10 age-matched non-hypoxic healthy volunteers (controls). All the examined pathological conditions induced hypoxia, with ARDS and COVID-19 depressing the hematopoietic response without remarkable effects on erythropoietin. Free iron was higher than the controls in all patients, with higher levels of hepcidin and soluble transferrin receptor in ARDS and COVID-19. All markers of the redox state and antioxidant barrier were overexpressed in ARDS and COVID-19. However, glutathionyl hemoglobin, a candidate marker for the redox imbalance, was especially low in ARDS, despite depressed levels of glutathione being present in all patients. Although iron regulation was dysfunctional in all groups, the depressed antioxidant barrier in ARDS, and to a lesser extent in COVID-19, might induce greater inflammatory responses with consequent anemia.

Original languageEnglish
Article number1460
JournalAntioxidants
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Acute hypoxia
  • Antioxidant barrier
  • Chronic hypoxia
  • Erythropoiesis
  • Hepcidin
  • Iron
  • Redox imbalance

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Differential redox state and iron regulation in chronic obstructive pulmonary disease, acute respiratory distress syndrome and coronavirus disease 2019'. Together they form a unique fingerprint.

Cite this