Aminothiols exchange in coronavirus disease 2019

Abstract

Objective: Clinical manifestation of the inflammatory process in its relation to biochemical markers (total cysteine [Cys], cysteine-glycine [CysGly], glutathione [GSH], glutamate-cysteine [Glu-Cys], homocysteine [Hcy], the ratio of reduced to oxidized glutathione [GSH/GSSG], the ratio of reduced to oxidized cysteine [CySH/CySS], malondialdehyde-oxidized low-density lipoproteins [MDA-oxLDL]) has been studied in patients with coronavirus disease 2019 (COVID-19). Material and methods: 48 patients with mild to severe COVID-19 and 20 healthy volunteers were included in our research. The participants were divided into 4 experimental groups according to inflammation intensity estimated based on the serum levels of interleukin 6 (IL-6). Results: All 4 groups showed the prevalence of male patients and elevated serum levels of IL-6 (by 54.6%). There was no comorbidity in patients with mild COVID-19 (nasopharyngitis symptoms) and in healthy control subjects. 50% of patients with lung damage had accompanying diseases. Alterations of aminoethyl metabolism were detected in COVID-19 patients: as reflected by the decreased levels of Cys, CysGly, and Glu-Cys and the increased levels of GSH as compared to the control group. Conclusion: Elevation of IL-6 over 7.5 pg/mL was associated with decreased GSH/GSSG and CySH/CySS ratios indicating enhanced oxidative stress and was followed by protein oxidation, specifically MDA-oxLDL.

Keywords

coronavirus disease 2019 / aminothiols / oxidative stress / interleukin-6 / oxidized lipoproteins

References

[1] Checconi P, DeAngelis M, Marcocci M E, et al. Redox-modulating agents in the treatment of viral infections. Int J Mol Sci, 2020; 21(11): 4084.

[2] Lavillette D, Barbouche R, Yao Y, et al. Significant redox insensitivity of the functions of the SARS-CoV spike glycoprotein: comparison with HIV envelope. J Biol Chem, 2006; 281(14): 9200-9204

[3] Fenouillet E, Barbouche R, Jones I M. Cell entry by enveloped viruses: redox considerations for HIV and SARS-coronavirus. Antioxid Redox Signal, 2007; 9(8): 1009-1034.

[4] Kryukov E V, Ivanov A V, Karpov V O, et al. Association of low molecular weight plasma aminothiols with the severity of Coronavirus disease 2019. Oxid Med Cell Longev, 2021; 2021: 9221693.

[5] Musaogullari A, Chai Y C. Redox regulation by protein S-glutathionylation: from molecular mechanisms to implications in health and disease. Int J Mol Sci, 2020; 21(21): 8113.

[6] Ghezzi P. Role of glutathione in immunity and inflammation in the lung. Int J Gen Med, 2011; 4: 105-113.

[7] Rochette L, Ghibu S. Mechanics insights of alpha-lipoic acid against cardiovascular diseases during COVID-19 infection. Int J Mol Sci, 2021; 22(15): 7979.

[8] Focks J J, Van Schaik A., Clappers N, et al. Assessment of plasma aminothiol levels and the association with recurrent atherothrombotic events in patients hospitalized for an acute coronary syndrome: a prospective study. Clin Chem Lab Med, 2013; 51(11): 2187-2193.

[9] Fefelova E V, Tereshkov P P, Maksimenya M V, et al. Human lymphocytes develop apoptosis when exposed with aminothyols in short-term cell culture. Transbaikalian Med Bulletin, 2016; 2: 98-106.

[10] The prevention, diagnosis and treatment of the new coronavirus infection 2019-nCoV. Temporary guidelines Ministry of Health of the Russian Federation. Pulmonologiya, 2019; 29(6): 655-672.

[11] Elesela S, Lukacs NW. Role of mitochondria in viral infections. Life, 2021; 11: 232.

[12] Alekseeva E I, Tepaev R F, Shilkrot I, et al. COVID-19-associated secondary hemophagocytic lymphohistiocytosis (the syndrome of "cytokine storm"). Annals of the Russian Academy of Medical Sciences, 2021; 76(1): 51-66.

[13] Khomich O A, Kochetkov S N, Bartosch B, et al. Redox biology of respiratory viral infections. Viruses, 2018; 10(8): 392.

[14] Rajagopalan S, Kurz S, Munzel T, et al. Angiotensin Ⅱ -mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest, 1996; 97: 1916-1923.

[15] Voronina T A. Antioxidants/antihypoxants: the missing puzzle piece in effective pathogenetic therapy for COVID-19. Infektsionnye bolezni, 2020; 2: 97-102.

[16] Mittal M, Siddiqui M, Tran K, et al. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal, 2014; 20(7): 1126-1167.

[17] Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. status of the art. Clin Interv Aging, 2018; 13: 757-772.

[18] Bin P, Huang R, Zhou X. Oxidation resistance of the sulfur amino acids: methionine and cysteine. Biomed Res Int, 2017; 2017: 9584932.

[19] Suhai S, Zajac J, Fossum C, et al. Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 (Covid-19) infection: a review. Protein J, 2020; 26: 1-13.

[20] Bartolini D, Wang Y, Zhang J, et al. Selenohormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities. PLoS ONE, 2019; 14(4): e0205626.

[21] Singh J, Dhindsa R S, Misra V, et al. SARS-CoV2 infectivity is potentially modulated by host redox status. Comput Struct Biotechnol J, 2020; 18: 3705-3711.