Aminothiols exchange in coronavirus disease 2019

Fefelova Elena Viktorovna; Karavaeva Tatyana Mikhailovna; Parshina Anastasia Anatolyevna; Ma Van De Vasilina Denisovna; Tereshkov Pavel Petrovich

doi:10.2478/fzm-2023-0006

Aminothiols exchange in coronavirus disease 2019

doi: 10.2478/fzm-2023-0006

1.
Department of Pathological Physiology, Chita State Medical Academy, Chita 672090, Russia
2.
Department of Chemistry and Biochemistry, Chita State Medical Academy, Chita 672090, Russia
3.
Department of Faculty Therapy, Chita State Medical Academy, Chita 672090, Russia
4.
Laboratory of Experimental and Clinical Biochemistry and Immunology, Chita State Medical Academy, Chita 672090, Russia

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Corresponding author: Fefelova Elena Viktorovna, E-mail: fefelova.elena@mail.ru

摘要

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

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Figure 1. Aminothyols in mild COVID-19

Cys, cysteine; CysGly, cysteine-glycine; GSH, glutathione; Hcy, homocysteine; Glu-Cys, glutamate-cysteine; COVID-19, coronavirus disease 2019.

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Table 1. Baseline characteristics of the patients with COVID-19

Indicator	1^st subgroup (N = 20)	2^nd subgroup (N = 10)	3^rd subgroup (N = 26)	4^th subgroup (N = 12)	Kruskal-Wallis test
Interleukin 6, pg/mL	2.25 (1.11, 3.55)	8.96 (7.17, 12.86)	15.48 (13.25, 23.46)^b	44.98 (35.50, 65.91)^{a, c}	χ² = 16.98 Р = 0.000 01
Gender (female/male), N	10/10	2/8	8/18	5/7	-
Age, years	43.00 (30.65, 50.20)	31.00 (27.75, 41.00)	46.00 (33.75, 52.20)	49.00 (44.00, 50.60)	χ² = 5.38 Р = 0.15
Chest computed tomography severity score	0 (0, 0)	0 (0, 0)	2 (1, 2)^a	3 (1, 4)^a	-
Body temperature, ℃	36.6 (35.5, 36.8)	36.8 (36.6, 37.65)^a	38.5 (37.68, 38.62)^{a, b}	38.6 (37.80, 38.92)^{a, b}	χ² = 13.20 Р = 0.004
Blood oxygen Saturation, %	99.80 (98.50, 99.90)	97.00 (96.25, 97.75)^a	95.50 (93.75, 97.20)^{a, b}	94.00 (93.00, 96.40)^a	χ² = 14.54 Р = 0.002
MDA-oxLDL	0 (0, 0.12)	8.66 (3.78, 11.60)^a	1.81 (0.50, 7.50)^a	0.49 (0.34, 2.87)^a	χ² = 15.34 Р = 0.002
Systolic blood pressure, mm Hg	120 (120, 130)	130 (115, 130)	130 (120, 145)	150 (150, 155) ^{a, c}	χ² = 13.48 Р = 0.004
Diastolic blood pressure, mm Hg	80 (75, 85)	80 (75, 85)	90 (80, 95)	90 (90, 95) ^{a, b}	χ² = 13.03 Р = 0.005
Atherosclerosis, %	-	-	20	17	-
Arterial hypertension, %	-	-	10	20	-
N, the number of patients; ^a, P < 0.05, vs. control group; ^b, P < 0.05, the 1^st subgroup vs. the 2^nd and the 3^rd subgroups; ^c, P < 0.05, the 3^rd subgroup vs. the 4^th group; COVID-19, coronavirus disease 2019.

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Table 2. Blood serum level of aminothiols in COVID-19 patients

Indicator	1^st subgroup (N = 20)	2^nd subgroup (N = 10)	3^rd subgroup (N = 26)	4^th subgroup (N = 12)	Kruskal–Wallis test
Cys, µmol/L	212.60 (167.70, 264.80)	207.67 (200.21, 235.45)^a	294.00 (271.72, 357.35)	173.24 (146.51, 329.17)^a	χ² = 10.49 Р = 0.01
CysGly, µmol/L	43.20 (39.50-53.90)	18.39 (13.74, 36.92)^a	17.37 (14.59, 33.37)^a	15.60 (10.43, 44.68)^a	χ² = 9.57 Р = 0.04
GSH, µmol/L	3.10 (2.60, 3.80)	3.25 (2.49, 4.35)	5.60 (4.71, 6.21)^a	7.85 (7.20, 9.24)^{a, c}	χ² = 13.93 Р = 0.003
Glu-Cys, µmol/L	3.20 (2.40-3.90)	6.99 (5.64, 7.84)^a	5.50 (5.12, 6.48)^a	3.89 (3.51, 8.00)^c	χ² = 12.21 Р = 0.007
Hcy, µmol/L	6.75 (5.77, 7.55)	9.97 (9.31, 10.22)^a	16.18 (13.28, 21.55)^{a, b}	15.94 (15.27, 19.61)^a	χ² = 16.36 Р = 0.000 01
GSH/GSSG	9.00 (8.97, 9.18)	0.10 (0.05, 0.19)^a	0.23 (0.14, 0.37)^a	0.25 (0.17, 0.27)^a	χ² = 12.08 Р = 0.004
CySH/CySS	1.67 (1.02, 1.88)	1.35 (1.22, 1.56)	0.59 (0.37, 0.69)	0.14 (0.06, 0.34)	χ² = 15.06 Р = 0.002
N, the number of patients; ^a, P < 0.05, vs. control group; ^b, P < 0.05, the 1^st subgroup vs. the 2^nd and the 3^rd subgroups; ^c, P < 0.05, the 3^rd subgroup vs. the 4^th group; Cys, cysteine; CysGly, cysteine-glycine; GSH, glutathione; Hcy, homocysteine; Glu-Cys, glutamate-cysteine; COVID-19, coronavirus disease 2019.

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参考文献(21)

[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. doi: 10.3390/ijms21114084
[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 doi: 10.1074/jbc.M512529200
[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. doi: 10.1089/ars.2007.1639
[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. doi: 10.3390/ijms21218113
[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. doi: 10.3390/ijms22157979
[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. doi: 10.1515/cclm-2013-0103
[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. doi: 10.3390/life11030232
[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. doi: 10.15690/vramn1410
[13]	Khomich O A, Kochetkov S N, Bartosch B, et al. Redox biology of respiratory viral infections. Viruses, 2018; 10(8): 392. doi: 10.3390/v10080392
[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. doi: 10.1172/JCI118623
[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. doi: 10.1089/ars.2012.5149
[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. doi: 10.2147/CIA.S158513
[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.