Metabolic transformation of oral fluid in COVID-19: the role of pro-inflammatory cytokines

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Introduction. In the context of the ongoing COVID-19 pandemic, studying all aspects of the impact of SARS-CoV-2 on the human body remains a priority. This article investigates changes in the oral fluid of patients with COVID-19, focusing on the relationship between pro-inflammatory cytokines and metabolic alterations.

Objective: To study the biochemical composition of oral fluid in COVID-19 patients and to identify the relationship between pro-inflammatory cytokines and potential metabolic changes.

Material and Methods. The study was conducted at the Samara State Medical University. Oral fluid from 157 COVID-19 patients (study group) and 89 healthy individuals (control group) was used as the research material. The following were determined in oral fluid: total protein content, albumin, C-reactive protein, metabolites (urea, uric acid, glucose, lactate), electrolytes, cytokines (interleukin-6, interleukin-8), and enzyme activity (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase). Statistical processing of the data was performed using the StatTech v. 4.8.7 software (developer – Stattech LLC, Russia).

Results. The study evaluated metabolic and immunological changes in the oral fluid of patients with COVID-19. A significant increase in the content of total protein, sodium, chlorine, calcium, magnesium, iron, as well as interleukins-6 and -8, C-reactive protein, and activity of creatine phosphokinase, gamma-glutamyl transpeptidase, and lactate dehydrogenase was revealed. An inverse correlation was established between the level of IL-6 and the activity of alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, concentration of urea and magnesium, which may indicate alternative mechanisms of COVID-19 pathogenesis in the oral cavity. A direct correlation was found between C-reactive protein and uric acid, likely associated with oxidative stress. IL-8 did not show significant relationships with the metabolic profile.

Conclusion. The results described above highlight the relationship between the immune response, metabolic status, and local processes occurring in the oral cavity. The identified patterns necessitate further in-depth research to study the molecular mechanisms of these relationships in detail. The knowledge gained can contribute to the search for potential biomarkers to assess disease severity, predict its outcome, and monitor the effectiveness of therapy, as well as to develop new therapeutic approaches aimed at modulating immune and metabolic disorders associated with COVID-19.

Full Text

Restricted Access

About the authors

I. A. Nazarkina

Samara State Medical University of the Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: bio-sam@yandex.ru
SPIN-code: 1926-3420

Assistant of the Department of Fundamental and Clinical Biochemistry with Laboratory Diagnostics

Russian Federation, 89 Chapaevskaya str., Samara, 443099

I. A. Selezneva

Samara State Medical University of the Ministry of Healthcare of the Russian Federation

Email: bio-sam@yandex.ru
ORCID iD: 0000-0001-6647-5330
SPIN-code: 5112-3841

Dr.Sc. (Med.), Associate Professor, Associate Professor of the Department of Clinical Biochemistry with Laboratory Diagnostics

Russian Federation, 89 Chapaevskaya str., Samara, 443099

F. N. Gilmiyarova

Samara State Medical University of the Ministry of Healthcare of the Russian Federation

Email: bio-sam@yandex.ru
ORCID iD: 0000-0002-5619-4583
SPIN-code: 7638-1812

Dr.Sc. (Med.), Professor, Honored Scientist of the Russian Federation, Professor of the Department of Fundamental and Clinical Biochemistry with Laboratory Diagnostics

Russian Federation, 89 Chapaevskaya str., Samara, 443099

V. V. Kartashov

Samara State Medical University of the Ministry of Healthcare of the Russian Federation

Email: stomkvv@gmail.com
ORCID iD: 0000-0002-8671-2898
SPIN-code: 7554-8410

Post-graduate Student of the Department of Orthopedic Dentistry

Russian Federation, 89 Chapaevskaya str., Samara, 443099

O. A. Baldina

Samara State Medical University of the Ministry of Healthcare of the Russian Federation

Email: bio-sam@yandex.ru
ORCID iD: 0000-0002-7566-2485
SPIN-code: 9767-4691

Ph.D. (Med.), Associate Professor, Associate Professor of the Department of Clinical Biochemistry with Laboratory Diagnostics

Russian Federation, 89 Chapaevskaya str., Samara, 443099

References

  1. Nazerian Y., Ghasemi M., Yassaghi Y. et al. Role of SARS-CoV-2-induced cytokine storm in multi-organ failure: Molecular pathways and potential therapeutic options. Int Immunopharmacol. 2022; 113(Pt B): 109428. doi: 10.1016/j.intimp.2022.109428.
  2. Yang L., Xie X., Tu Z. et al. The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduct Target Ther. 2021; 6(1): 255. doi: 10.1038/s41392-021-00679-0.
  3. Levinson T., Wasserman A. C-Reactive Protein Velocity (CRPv) as a New Biomarker for the Early Detection of Acute Infection/Inflammation. Int J Mol Sci. 2022; 23(15): 8100. doi: 10.3390/ijms23158100.
  4. Lehrskov L.L, Christensen R.H. The role of interleukin-6 in glucose homeostasis and lipid metabolism. Semin Immunopathol. 2019; 41(4): 491–499. doi: 10.1007/s00281-019-00747-2.
  5. Nijakowski K., Gruszczyński D., Kopała D. et al. Salivary Metabolomics for Oral Squamous Cell Carcinoma Diagnosis: A Systematic Review. Metabolites. 2022; 12(4): 294. doi: 10.3390/metabo12040294.
  6. Del Valle D.M., Kim-Schulze S., Huang H.H. et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020; 26(10): 1636–1643. doi: 10.1038/s41591-020-1051-9.
  7. Zoppini G., Cacciatori V., Negri C. et al. The aspartate aminotransferase-to-alanine aminotransferase ratio predicts all-cause and cardiovascular mortality in patients with type 2 diabetes. Medicine (Baltimore). 2016; 95(43): e4821. doi: 10.1097/MD.0000000000004821.
  8. Xu L., Liu J., Lu M. et al. Liver injury during highly pathogenic human coronavirus infections. Liver Int. 2020; 40(5): 998-1004. doi: 10.1111/liv.14435.
  9. Chamorey A.L., Magné N., Pivot X., Milano G. Impact of glycosylation on the effect of cytokines. A special focus on oncology. Eur Cytokine Netw. 2002; 13(2): 154–160.
  10. Majnarić L.T., Bosnić Z., Štefanić M., Wittlinger T. Cross-Talk between the Cytokine IL-37 and Thyroid Hormones in Modulating Chronic Inflammation Associated with Target Organ Damage in Age-Related Metabolic and Vascular Conditions. Int J Mol Sci. 2022; 23(12): 6456. doi: 10.3390/ijms23126456.
  11. Wallimann T., Wyss M., Brdiczka D. et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochemical Journal. 1992; 281(Pt 1): 21–40.
  12. Schlattner U., Kay L., Tokarska-Schlattner M. Mitochondrial Proteolipid Complexes of Creatine Kinase. Subcell Biochem. 2018; 87: 365–408. doi: 10.1007/978-981-10-7757-9_13.
  13. Серебренникова С.Н., Семинский И.Ж., Гузовская Е.В. и др. Воспаление – фундаментальный патологический процесс: лекция 1 (альтерация, сосудистые реакции). Байкальский медицинский журнал. 2023; 2(2): 53–64. [Serebrennikova S.N., Seminskiy I.Zh., Guzovskaya E.V. et al. Inflammation – a fundamental pathological process: lecture 1 (alteration, vascular reactions). Baykalskiy meditsinskiy zhurnal. 2023; 2(2): 53–64. (In Russ.)]. doi: 10.57256/2949-0715-2023-2-53-64.
  14. Chen Y.Y., Clancy K.A., Burne R.A. Streptococcus salivarius urease: genetic and biochemical characterization and expression in a dental plaque streptococcus. Infect Immun. 1996; 64(2): 585–592. doi: 10.1128/iai.64.2.585-592.1996.
  15. Guerrero-Romero F., Micke O., Simental-Mendía LE. et al. Importance of Magnesium Status in COVID-19. Biology (Basel). 2023; 12(5): 735. doi: 10.3390/biology12050735.
  16. Mazur A., Maier J.A., Rock E. et al. Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys. 2007; 458(1): 48–56. doi: 10.1016/j.abb.2006.03.031.
  17. Jan M.I., Khan R.A., Fozia et al. C-Reactive Protein and High-Sensitive Cardiac Troponins Correlate with Oxidative Stress in Valvular Heart Disease Patients. Oxid Med Cell Longev. 2022; 2022: 5029853. doi: 10.1155/2022/5029853.
  18. Tian R., Yang C., Chai SM. et al. Evolutionary impacts of purine metabolism genes on mammalian oxidative stress adaptation. Zool Res. 2022; 43(2): 241–254. doi: 10.24272/j.issn.2095–8137.2021.420.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Russkiy Vrach Publishing House