A decrease in the concentration of free blood glutathione in the acute phase of coronavirus infection

Aim of the study: to investigate the dynamics of glutathione metabolite concentrations in the blood of patients during the acute phase of coronavirus infection, as well as their dependencies on each other, on NAD⁺ metabolites, the severity of the infl ammatory response, and pre-existing conditions. Materials and methods. Changes in the concentration of oxidized and reduced forms of glutathione and their ratio, as well as clinical and biochemical parameters, including NAD⁺ and NADPH⁺ metabolites, were analyzed in patients with new coronavirus infection COVID-19 during the acute phase. Results. A signifi cant decrease in the concentration of both reduced and oxidized forms of glutathione and an increase in the ratio of reduced to oxidized forms compared to the control were demonstrated. A positive correlation was noted between the severity of respiratory failure and the oxidized form of glutathione and NADPH⁺. The reduced form of glutathione had a positive correlation with the concentration of NAD⁺ and NADPH⁺ and a negative correlation with the presence of obesity and ferritin concentration. Conclusion. For the fi rst time, a decrease in the concentration of key components of the cell’s antioxidant defense system — glutathione system — has been shown in patients with COVID-19, opening up prospects for the development of treatment methods for patients in the active phase using sulfhydryl group donors.

1. Akerboom T.P., Bilzer M., Sies H. The relationship of biliary glutathione disulfi de effl ux and intracellular glutathione disulfi de content in perfused rat liver. J. Biol. Chem. 1982;257(8):4248– 4252.

2. Fang Y.Z., Yang S., Wu G. Free radicals, antioxidants, and nutrition. Nutrition. 2002;18(10):872–9. DOI: 10.1016/s0899-9007(02)00916-4. PMID: 12361782

3. Wang Y., Yen F.S., Zhu X.G. et al. SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. Nature. 2021;599(7883):136–140. DOI: 10.1038/s41586-021-04025-w

4. Sies H. Glutathione and its role in cellular functions. Free Radic. Biol. Med. 1999;27(9–10):916–921. DOI: 10.1016/s0891- 5849(99)00177-x

5. Zhang H., Forman H.J. Glutathione synthesis and its role in redox signaling. Semin. Cell Dev. Biol. 2012;23(7):722–728. DOI: 10.1016/j.semcdb.2012.03.017

6. Tiku V., Tan M., Dikic I. Mitochondrial Functions in Infection and Immunity. Trends Cell Biol. 2020;30(9):748. DOI: 10.1016/j. tcb.2020.07.001

7. Guzzi P., Mercatelli D., Ceraolo C., Giorgi F. Master Regulator Analysis of the SARS-CoV-2/Human Interactome. J. Clin. Med. 2020;9(4):982. DOI: 10.3390/jcm9040982

8. Jones D.P. Redefi ning oxidative stress. Antioxid. Redox Signal. 2006;8(9–10):1865–1879. DOI: 10.1089/ars.2006.8.1865

9. Gloire G., Piette J. Redox regulation of nuclear post-translational modifi cations during NF-kappaB activation. Antioxid. Redox Signal. 2009;11(9):2209–2222. DOI: 10.1089/ars.2009.2463

10. Rodionov G.G., Xurcilava O.G., Pluzhnikov N.N. et al. Oxidative stress and infl ammation: a pathogenetic partnership. Sankt-Peterburg, Se ve ro-Zapadny`j gosudarstvenny`j medicinskij universitet im. I.I. Mech ni kova, 2012 ;340:40. (In Russian). ISBN 978-5-89588- 048-7. EDN RXCYBH

11. Rossi R., Milzani A., Dalle-Donne I. et al. Blood glutathione disulfi de: in vivo factor or in vitro artifact? Clin. Chem. 2002;48(5):742–753.

12. Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal. Biochem. 1969;27(3):502– 522. DOI:10.1016/0003-2697(69)90064-5

13. Shaik I.H., Mehvar R. Rapid determination of reduced and oxidized glutathione levels using a new thiol-masking reagent and the enzymatic recycling method: application to the rat liver and bile samples. Anal. Bioanal. Chem. 2006;385(1):105–113. DOI:10.1007/s00216-006-0375-8

14. Luk`yanova L.D. Modern problems of adaptation to hypoxia. Signaling mechanisms and their role in systemic regulation. Patofi ziologiya i e`ksperimtntaknaya terapiya. 2011:1:3 –19. (In Russian).

15. Kolevatova L.A., Alekh no vich A.V., Gulyaev N.I., Prokhorchik А.А., Euro L.L. A de - crease in NAD+ metabolites in the blood of patients in the acute phase of a new corona virus infection as an indicator of a systemic dis order of energy meta bolism and an indicator of possible therapeutic effects. Gospital`naya medicina: nauka i praktika. 2023;6(2):48–57. (In Russian). DOI: 10.34852/GM3CVKG.2023.95.75.017. EDN CKEHTW

16. Shi Z., Puyo C.A. N-acetylcysteine to combat COVID-19: an evidence review. Ther. Clin. Risk Manag. 2020;16:1047–1055. Published 2020 Nov 2. DOI:10.2147/TCRM.S273700

17. Faverio P., Rebora P., Rossi E. et al. Impact of N-acetyl-l-cysteine on SARS-CoV-2 pneumonia and its sequelae: results from a large cohort study. ERJ Open Res. 2021;8(1):00542–2021. Published 2021 Feb 7. DOI: 10.1183/23120541.00542-2021