Evaluation of the Relationship Between Aquaporin-1, Hepcidin, Zinc, Copper, and İron Levels and Oxidative Stress in the Serum of Critically Ill Patients with COVID-19
Nihayet Bayraktar, Mustafa Bayraktar, Ali Ozturk, Bashar Ibrahim
Biological Trace Element Research, doi:10.1007/s12011-022-03400-6
Our study aims to determine the relationship between hepcidin, aquaporin (AQP-1), copper (Cu), zinc (Zn), iron (Fe) levels, and oxidative stress in the sera of seriously ill COVID-19 patients with invasive mechanical ventilation. Ninety persons with and without COVID-19 were taken up and separated into two groups. The first group included seriously COVID-19 inpatients having endotracheal intubation in the intensive care unit (n = 45). The second group included individuals who had negative PCR tests and had no chronic disease (the healthy control group n = 45). AQP-1, hepcidin, Zn, Cu, Fe, total antioxidant status (TAS), and total oxidant status (TOS) were studied in the sera of both groups, and the relations of these levels with oxidative stress were determined. When the COVID-19 patient and the control groups were compared, all studied parameters were found to be statistically significant (p < 0.01). Total oxidant status (TOS), oxidative stress index (OSI), and AQP-1, hepcidin, and Cu levels were increased in patients with COVID-19 compared to healthy people. Serum TAC, Zn, and Fe levels were found to be lower in the patient group than in the control group. Significant correlations were detected between the studied parameters in COVID-19 patients. Results indicated that oxidative stress may play an important role in viral infection due to SARS-CoV-2. We think that oxidative stress parameters as well as some trace elements at the onset of COVID-19 disease will provide a better triage in terms of disease severity.
Declarations Ethics Approval This study was approved by the local ethics committee of Harran University and the Ministry of Health of Turkey (18/01/2020-HRU/210231).
Consent to Participate All patients signed an informed consent for inclusion of personal records in the local database and for use to scientifc research purposes. Consent for Publication Not applicable.
Conflict of Interest The authors declare no competing interests.
References
Adam, Wijeratne, Rogler, Diaz, Quist et al., Synthetic Fe/Cu complexes: toward understanding heme-copper oxidase structure and function, Chem Rev,
doi:10.1021/acs.chemrev.8b00074Bakhshandeh, Sorboni, Javanmard, Mottaghi, Mehrabi et al., Variants in ACE2; potential influences on virus infection and COVID-19 severity, InInfect Genet Evol,
doi:10.1016/j.meegid.2021.104773Cao, Prior, Comparison of different analytical methods for assessing total antioxidant capacity of human serum Automation and Analytical Techniques, Clin Chem
Cárdenas-Rodríguez, Bandala, Vanoye-Carlo, Mejía, Gómez-Manzo et al., Use of antioxidants for the neuro-therapeutic management of covid-19, Antioxidants,
doi:10.3390/antiox10060971De Jesus, De, Andrade, Understanding the relationship between viral infections and trace elements from a metallomics perspective: ımplications for COVID-19, Metallomics,
doi:10.1039/d0mt00220hEhsani, COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein, Biol Direct,
doi:10.1186/s13062-020-00275-2Fedele, De Francesco, Riso, Collo, Obesity, malnutrition, and trace element deficiency in the coronavirus disease (COVID-19) pandemic: an overview, Nutrition,
doi:10.1016/j.nut.2020.111016Forman, Zhang, Targeting oxidative stress in disease: promise and limitations of antioxidant therapy, Nat Rev Drug Discov,
doi:10.1038/s41573-021-00233-1Hunter, Fulton, Ganz, Vogel, The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis, J Biol Chem,
doi:10.1074/jbc.M205305200Ibekwe, Fasunla, Orimadegun, Systematic review and meta-analysis of smell and taste disorders in COVID-19, OTO Open,
doi:10.1177/2473974X20957975Kelley, Daudu, Taylor, Mackey, Turniund, Effects of low-copper diets on human immune response, Am J Clin Nutr,
doi:10.1093/ajcn/62.2.412Mariajoseph-Antony, Kannan, Panneerselvam, Loganathan, Anbarasu et al., Could aquaporin modulators be employed as prospective drugs for COVID-19 related pulmonary comorbidity?, Med Hypotheses,
doi:10.1016/j.mehy.2020.110201Nai, Lorè, Pagani, Lorenzo, Modica et al., Hepcidin levels predict Covid19 severity and mortality in a cohort of hospitalized Italian patients, Am J Hematol,
doi:10.1002/ajh.26027Nemeth, Valore, Territo, Schiller, Lichtenstein et al., Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein, Blood,
doi:10.1182/blood-2002-10Pathangey, Fadadu, Hospodar, Abbas, Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies, Am J Physiol Lung Cell Mol Physiol,
doi:10.1152/AJPLUNG.00259.2020Pecora, Persico, Argentiero, Neglia, Esposito, The role of micronutrients in support of the immune response against viral infections, Nutrients,
doi:10.3390/nu12103198Rani, Goyal, Bhatnagar, Manhas, Goel et al., Potential molecular mechanisms of zinc-and coppermediated antiviral activity on COVID-19, Nutr Res,
doi:10.1016/j.nutres.2021.05.008Schönrich, Raftery, Samstag, Devilishly radical NETwork in COVID-19: oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression, Adv Biol Regul,
doi:10.1016/j.jbior.2020.100741Sharif-Askari, Sharif-Askari, Mdkhana, Alsayed, Alsafar et al., Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection, Free Radical Biol Med,
doi:10.1016/j.freeradbiomed.2021.06.018Skalny, Timashev, Aschner, Aaseth, Chernova et al., Serum zinc, copper, and other biometals are associated with COVID-19 severity markers, Metabolites,
doi:10.3390/metabo11040244Stafford, Bokil, Achard, Kapetanovic, Schembri et al., Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper, Biosci Rep,
doi:10.1042/BSR20130014Suhail, Zajac, Fossum, Lowater, Mccracken et al., Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) ınfection: a review, Protein J,
doi:10.1007/s10930-020-09935-8Tu, Yang, Zhou, Wen, Li et al., Risk factors for mortality of critically ill patients with covid-19 receiving invasive ventilation, Int J Med Sci,
doi:10.7150/ijms.50039Wacewicz, Socha, Soroczyńska, Niczyporuk, Aleksiejczuk et al., Concentration of selenium, zinc, copper, Cu/Zn ratio, total antioxidant status and c-reactive protein in the serum of patients with psoriasis treated by narrow-band ultraviolet B phototherapy: a case-control study, J Trace Elem Med Biol,
doi:10.1016/j.jtemb.2017.06.008Wang, Ding, Gao, Li, Shen et al., The interactions of aquaporins and mineral nutrients in higher plants, Int J Mol Sci,
doi:10.3390/ijms17081229Zhang, Ju, Ma, Wang, N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia, Medicine (Baltimore),
doi:10.1097/MD.0000000000013087Zhang, Yan, Fan, Liu, Liu et al., D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19, J Thromb Haemost,
doi:10.1111/jth.14859
