Severity-related differences on response of antioxidant defense system in COVID-19 patients

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Abstract

Background. COVID-19 is a major human infectious disease with devastating economic and public health impacts globally. Oxidative stress plays a pivotal role in the pathogenesis and progression of various viral infections. The aim of the present study was to evaluate oxidative stress biomarkers in COVID-19 patients with different severity to healthy participants. Materials and methods. This case-control study was conducted on 60 patients with COVID-19 infection (30 moderate and 30 severe) and 30 matched healthy controls referred to Baqiyatallah Hospital, Tehran from March until July 2020. Serum levels of total antioxidant capacity (TAC) and oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and levels of glutathione (GSH) and malondialdehyde (MDA) were measured using biochemical methods. Results. In terms of gender, the healthy control group consisted of 17 males and 13 females, and the group of moderate patients included 20 males and 10 females and severe COVID-19 patients included 14 males and 16 females, which were not statistically significant (p = 0.295). Also, the mean age in severe COVID-19 patients (46.6±12.8) was not significantly different from the healthy control (43.8±12; p = 0.683) and moderate (45.60±13.30; p = 0.953) groups. The results showed that SOD and CAT activities and MDA level in moderate and severe of COVID-19 patients were higher than the healthy individuals, while GPx and GR activities and GSH and TAC levels were significantly lower. SOD and GPx activities and MDA level in severe of COVID-19 patients were significantly different from moderate patients. However, CAT and GR activities and TAC level in severe cases was not significantly different from moderate patients. Conclusion. Oxidative stress plays an important role in the pathogenesis of COVID-19 infection as indicated by the enhancement of lipid peroxidation, depletion of GSH and alteration in antioxidant enzymes. The systemic oxidative stress is directly related to the severity of the pathogenesis. Therefore, substances with antioxidant properties may be a potential choice for the treatment of COVID-19 infection.

About the authors

M. Shohrati

Baqiyatallah University of Medical Sciences

Email: majidshohrati@yahoo.com

PhD, Professor of Pharmacology, Department of Clinical Pharmacy, Faculty of Pharmacy

Iran, Islamic Republic of, Tehran

Mahvash Jafari

Baqiyatallah University of Medical Sciences

Author for correspondence.
Email: m.jafari145@gmail.com

PhD, Professor of Biochemistry, Department of Biochemistry, Faculty of Medicine

Iran, Islamic Republic of, Tehran

M. Sadrzadeh

Baqiyatallah University of Medical Sciences

Email: masoudsadr5468@gmail.com

Dr. in Pharmacology, Department of Clinical Pharmacy, Faculty of Pharmacy

Iran, Islamic Republic of, Tehran

H. Ebrahiminezhad

Baqiyatallah University of Medical Sciences

Email: hamidrezaebi@yahoo.com

Dr. in Pharmacology, Department of Clinical Pharmacy, Faculty of Pharmacy

Iran, Islamic Republic of, Tehran

M. Ghanei

Baqiyatallah University of Medical Sciences

Email: mghaneister@gmail.com

MD, Professor, Pulmonologist, Chemical Injuries Research Center

Iran, Islamic Republic of, Tehran

References

  1. Atanasovska E., Petrusevska M., Zendelovska D., Spasovska K., Stevanovikj M., Kasapinova K., Gjorgjievska K., Labachevski N. Vitamin D levels and oxidative stress markers in patients hospitalized with COVID-19. Redox Rep., 2021, vol. 26, no. 1, pp. 184–189. doi: 10.1080/13510002.2021.1999126
  2. Badawy M.A., Yasseen B.A., El-Messiery R.M., Abdel-Rahman E.A., Elkhodiry A.A., Kamel A.G., El-Sayed H., Shedra A.M., Hamdy R., Zidan M., Al-Raawi D., Hammad M., Elsharkawy N., El Ansary M., Al-Halfawy A., Elhadad A., Hatem A., Abouelnaga S., Dugan L.L., Ali S.S. Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality. Elife, 2021, vol. 10: e69417. doi: 10.7554/eLife.69417
  3. Beltrán-García J., Osca-Verdegal R., Pallardó F.V., Ferreres J., Rodríguez M., Mulet S., Sanchis-Gomar F., Carbonell N., García-Giménez J.L. Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression. Antioxidants (Basel), 2020, vol. 9, no. 10, pp. 936–953. doi: 10.3390/antiox9100936
  4. Chernyak B.V., Popova E.N., Prikhodko A.S., Grebenchikov O.A., Zinovkina L.A., Zinovkin R.A. COVID-19 and Oxidative Stress. Biochemistry (Mosc.), 2020, vol. 85, no. 12, pp. 1543–1553. doi: 10.1134/S0006297920120068
  5. Chiscano-Camón L., Ruiz-Rodriguez J.C., Ruiz-Sanmartin A., Roca O., Ferrer R. Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit. Care, 2020, vol. 24, no. 1, pp. 522–530. doi: 10.1186/s13054-020-03249-y
  6. Cullen S. Oxidative Marker Changes in COVID-19 Patients. J. Health Med. Res., 2022, vol. 4, no. 1: 102. doi: 10.35248/jhmr.22.04(01).102
  7. Eshrati R., Jafari M., Gudarzi S., Nazari A., Samizadeh E., Ghafourian Hesami M. Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-induced oxidative stress in rat liver and kidney. J. Biochem., 2021, vol. 169, no. 3, pp. 337–350. doi: 10.1093/jb/mvaa107
  8. Forcados G.E., Muhammad A., Oladipo O.O., Makama S., Meseko C.A. Metabolic Implications of Oxidative Stress and Inflammatory Process in SARS-CoV-2 Pathogenesis: Therapeutic Potential of Natural Antioxidants. Front. Cell. Infect. Microbiol., 2021, vol. 11: 654813. doi: 10.3389/fcimb.2021.654813
  9. Golabi S., Ghasemi S., Adelipour M., Bagheri R., Suzuki K., Wong A., Seyedtabib M., Naghashpour M. Oxidative Stress and Inflammatory Status in COVID-19 Outpatients: A Health Center-Based Analytical Cross-Sectional Study. Antioxidants (Basel), 2022, vol. 11, no. 4, pp. 606–620. doi: 10.3390/antiox11040606
  10. Gudarzi S., Jafari M., Pirzad Jahromi G., Eshrati R., Asadollahi M., Nikdokht P. Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: a randomized clinical trial. Nutr. Neurosci., 2022, vol. 25, no. 6, pp. 1137–1146. doi: 10.1080/1028415X.2020.1840118
  11. Guloyan V., Oganesian B., Baghdasaryan N., Yeh C., Singh M., Guilford F., Ting Y.S., Venketaraman V. Glutathione Supplementation as an Adjunctive Therapy in COVID-19. Antioxidants (Basel), 2020, vol. 9, no. 10, pp. 914–927. doi: 10.3390/antiox9100914
  12. Handu D., Moloney L., Rozga M., Cheng F.W. Malnutrition Care During the COVID-19 Pandemic: Considerations for Registered Dietitian Nutritionists. J. Acad. Nutr. Diet., 2021, vol. 121, no. 5, pp. 979–987. doi: 10.1016/j.jand.2020.05.012
  13. Heydari J., Jafari M., Khazaie S., Goosheh H., Ghanei M., Karbasi A. The role of oxidative stress in severity of obstructive pulmonary complications in sputum of sulfur mustard-injured patients. Iran J. Toxicol., 2017, vol. 11, no. 5, pp. 5–11.
  14. Jafari M., Salehi M., Shirbazou S., Abasian L., Talebi-Meymand F. Evaluation of gender-related differences in response to oxidative stress in Toxoplasma gondii positive serum. Ann. Mil. Health Sci. Res., 2014, vol. 12, no. 2: e63369.
  15. Jaiswal N., Bhatnagar M., Shah H. N-acetycysteine: A potential therapeutic agent in COVID-19 infection. Med. Hypotheses, 2020, vol. 144: 110133. doi: 10.1016/j.mehy.2020.110133
  16. Karkhanei B., Talebi Ghane E., Mehri F. Evaluation of oxidative stress level: total antioxidant capacity, total oxidant status and glutathione activity in patients with COVID-19. New Microbes New Infect., 2021, vol. 42: 100897. doi: 10.1016/j.nmni.2021.100897
  17. Khan S., Faisal S., Usman H., Zainab R., Taj F., Amrani R., Tayyeb M. COVID-19: a brief overview on the role of vitamins specifically vitamin C as immune modulators and in prevention and treatment of SARS-Cov-2 infections. Biomed. J. Sci. Tech. Res., 2020, vol. 28, no. 3, pp. 21580–21586. doi: 10.26717/BJSTR.2020.28.004648
  18. Khazaie S., Jafari M., Heydari J., Asgari A., Tahmasebi K., Salehi M., Abedini M.S. Modulatory effects of vitamin C on biochemical and oxidative changes induced by acute exposure to diazinon in rat various tissues: Prophylactic and therapeutic roles. J. Anim. Physiol. Anim. Nutr. (Berl)., 2019, vol. 103, no. 5, pp. 1619–1628. doi: 10.1111/jpn.13144
  19. Liao Q.J., Ye L.B., Timani K.A., Zeng Y.C., She Y.L., Ye L., Wu Z.H. Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus. Acta Biochim. Biophys. Sin. (Shanghai), 2005, vol. 37, no. 9, pp. 607–612. doi: 10.1111/j.1745-7270.2005.00082.x
  20. Martín-Fernández M., Aller R., Heredia-Rodríguez M., Gómez-Sánchez E., Martínez-Paz P., Gonzalo-Benito H., Sánchez-de Prada L., Gorgojo Ó., Carnicero-Frutos I., Tamayo E., Tamayo-Velasco Á. Lipid peroxidation as a hallmark of severity in COVID-19 patients. Redox Biol., 2021, vol. 48: 102181. doi: 10.1016/j.redox.2021.102181
  21. Meftahi G.H., Bahari Z., Jangravi Z., Iman M. A vicious circle between oxidative stress and cytokine storm in acute respiratory distress syndrome pathogenesis at COVID-19 infection. Ukr. Biochem. J., 2021, vol. 93, no. 1, pp. 18–29. doi: 10.15407/ubj93.01.018
  22. Mehri F., Rahbar A.H., Ghane E.T., Souri B., Esfahani M. Changes in oxidative markers in COVID-19 patients. Arch. Med. Res., 2021, vol. 52, no. 8, pp. 843–849. doi: 10.1016/j.arcmed.2021.06.004
  23. Mousavi S.R., Jafari M., Rezaei S., Agha-Alinejad H., Sobhani V. Evaluation of the effects of different intensities of forced running wheel exercise on oxidative stress biomarkers in muscle, liver and serum of untrained rats. Lab. Anim. (NY), 2020, vol. 49, no. 4, pp. 119–125. doi: 10.1038/s41684-020-0503-7
  24. Muhammad Y., Kani Y.A., Iliya S., Muhammad J.B., Binji A., El-Fulaty Ahmad A., Kabir M.B., Umar Bindawa K., Ahmed A. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med., 2021, vol. 9: 2050312121991246. doi: 10.1177/2050312121991246
  25. Naghashpour M., Ghiassian H., Mobarak S., Adelipour M., Piri M., Seyedtabib M., Golabi S. Profiling serum levels of glutathione reductase and interleukin-10 in positive and negative-PCR COVID-19 outpatients: A comparative study from southwestern Iran. J. Med. Virol., 2022, vol. 94, no. 4, pp. 1457–1464. doi: 10.1002/jmv.27464
  26. Poe F.L., Corn J. N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2. Med. Hypotheses, 2020, vol. 143: 109862. doi: 10.1016/j.mehy.2020.109862
  27. Polonikov A. Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients. ACS Infect. Dis., 2020, vol. 6, no. 7, pp. 1558–1562. doi: 10.1021/acsinfecdis.0c00288
  28. Qin M., Cao Z., Wen J., Yu Q., Liu C., Wang F., Zhang J., Yang F., Li Y., Fishbein G., Yan S., Xu B., Hou Y., Ning Z., Nie K., Jiang N., Liu Z., Wu J., Yu Y., Li H., Zheng H., Li J., Jin W., Pang S., Wang S., Chen J., Gan Z., He Z., Lu Y. An Antioxidant Enzyme Therapeutic for COVID-19. Adv. Mater., 2020, vol. 32, no. 43: e2004901. doi: 10.1002/adma.202004901
  29. Shakoor H., Feehan J., Al Dhaheri A.S., Ali H.I., Platat C., Ismail L.C., Apostolopoulos V., Stojanovska L. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas, 2021, vol. 143, pp. 1–9. doi: 10.1016/j.maturitas.2020.08.003
  30. Strycharz-Dudziak M., Kiełczykowska M., Drop B., Świątek Ł., Kliszczewska E., Musik I., Polz-Dacewicz M. Total Antioxidant Status (TAS), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) in Oropharyngeal Cancer Associated with EBV Infection. Oxid. Med. Cell. Longev., 2019, vol. 2019: 5832410. doi: 10.1155/2019/5832410
  31. Suhail S., Zajac J., Fossum C., Lowater H., McCracken C., Severson N., Laatsch B., Narkiewicz-Jodko A., Johnson B., Liebau J., Bhattacharyya S., Hati S. Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review. Protein J., 2020, vol. 39, no. 6, pp. 644–656. doi: 10.1007/s10930-020-09935-8
  32. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med., 2020, vol. 8, no. 4, pp. 420–422. doi: 10.1016/S2213-2600(20)30076-X
  33. Yaghoubi N., Youssefi M., Jabbari Azad F., Farzad F., Yavari Z., Zahedi Avval F. Total antioxidant capacity as a marker of severity of COVID-19 infection: Possible prognostic and therapeutic clinical application. J. Med. Virol., 2022, vol. 94, no. 4, pp. 1558–1565. doi: 10.1002/jmv.27500
  34. Zhang Y., Xu C., Agudelo Higuita N.I., Bhattacharya R., Chakrabarty J.H., Mukherjee P. Evaluation of I-TAC as a potential early plasma marker to differentiate between critical and non-critical COVID-19. Cell Stress, 2021, vol. 6, no. 1, pp. 6–16. doi: 10.15698/cst2022.01.262

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