Direct Application of 3-Maleimido-PROXYL for Proving Hypoalbuminemia in Cases of SARS-CoV-2 Infection: The Potential Diagnostic Method of Determining Albumin Instability and Oxidized Protein Level in Severe COVID-19

Ekaterina Georgieva; Vasil Atanasov; Rositsa Kostandieva; Vanya Tsoneva; Mitko Mitev; Georgi Arabadzhiev; Yovcho Yovchev; Yanka Karamalakova; Galina Nikolova

doi:10.3390/ijms24065807

Direct Application of 3-Maleimido-PROXYL for Proving Hypoalbuminemia in Cases of SARS-CoV-2 Infection: The Potential Diagnostic Method of Determining Albumin Instability and Oxidized Protein Level in Severe COVID-19

Int J Mol Sci. 2023 Mar 18;24(6):5807. doi: 10.3390/ijms24065807.

Authors

Ekaterina Georgieva^{1

2}, Vasil Atanasov³, Rositsa Kostandieva³, Vanya Tsoneva⁴, Mitko Mitev⁵, Georgi Arabadzhiev⁶, Yovcho Yovchev⁶, Yanka Karamalakova², Galina Nikolova²

Affiliations

¹ Department of "General and Clinical Pathology, Forensic Medicine, Deontology and Dermatovenerology", Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria.
² Department of "Medical Chemistry and Biochemistry", Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria.
³ Forensic Toxicology Laboratory, Military Medical Academy, 3 G. Sofiiski, 1606 Sofia, Bulgaria.
⁴ Department of Propaedeutics of Internal Medicine and Clinical Laboratory, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria.
⁵ Department of "Diagnostic Imaging", University Hospital "Prof. Dr. St. Kirkovich", 6000 Stara Zagora, Bulgaria.
⁶ Department of "Surgery and anesthesiology", University Hospital "Prof. Dr. St. Kirkovich", 6000 Stara Zagora, Bulgaria.

Abstract

Oxidative stress and the albumin oxidized form can lead to hypoalbuminemia, which is a predisposing factor for reduced treatment effectiveness and an increased mortality rate in severe COVID-19 patients. The aim of the study is to evaluate the application of free radical 3-Maleimido-PROXYL and SDSL-EPR spectroscopy in the in vitro determination of ox/red HSA in serum samples from patients with SARS-CoV-2 infection. Venous blood was collected from patients intubated (pO₂ < 90%) with a positive PCR test for SARS-CoV-2 and controls. At the 120th minute after the incubation of the serum samples from both groups with the 3-Maleimido-PROXYL, the EPR measurement was started. The high levels of free radicals were determined through the nitroxide radical TEMPOL, which probably led to increased oxidation of HSA and hypoalbuminemia in severe COVID-19. The double-integrated spectra of 3-Maleimido-PROXYL radical showed a low degree of connectivity due to high levels of oxidized albumin in COVID-19 patients. The low concentrations of reduced albumin in serum samples partially inhibit spin-label rotation, with A_max values and ΔH₀ spectral parameters comparable to those of 3-Maleimido-PROXYL/DMSO. Based on the obtained results, we suggest that the stable nitroxide radical 3-Maleimido-PROXYL can be successfully used as a marker to study oxidized albumin levels in COVID-19.

Keywords: 3-maleimido-PROXYL; COVID-19; EPR; ROS; TEMPOL; hypoalbuminemia.

MeSH terms

Albumins
COVID-19 Testing
COVID-19* / diagnosis
Free Radicals
Humans
Hypoalbuminemia* / diagnosis
SARS-CoV-2

Substances

nitroxyl
Free Radicals
Albumins

Grants and funding

This research was funded by the scientific project No.1/2020, 4/2022 of the Medical Faculty, Trakia University, Bulgaria, and Ministry of Education and Science BG-RRP-2.004-0006”Development of research and innovation at Trakia University in service of health and sustainable well-being”.