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{ 'indexed': {'date-parts': [[2022, 8, 24]], 'date-time': '2022-08-24T10:17:22Z', 'timestamp': 1661336242291},
'reference-count': 36,
'publisher': 'Springer Science and Business Media LLC',
'license': [ { 'start': { 'date-parts': [[2022, 8, 24]],
'date-time': '2022-08-24T00:00:00Z',
'timestamp': 1661299200000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.springer.com/tdm'},
{ 'start': { 'date-parts': [[2022, 8, 24]],
'date-time': '2022-08-24T00:00:00Z',
'timestamp': 1661299200000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://www.springer.com/tdm'}],
'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False},
'DOI': '10.1007/s12011-022-03400-6',
'type': 'journal-article',
'created': {'date-parts': [[2022, 8, 24]], 'date-time': '2022-08-24T07:10:28Z', 'timestamp': 1661325028000},
'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': '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',
'prefix': '10.1007',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-5745-9678',
'authenticated-orcid': False,
'given': 'Nihayet',
'family': 'Bayraktar',
'sequence': 'first',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-0352-0904',
'authenticated-orcid': False,
'given': 'Mustafa',
'family': 'Bayraktar',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-2428-1831',
'authenticated-orcid': False,
'given': 'Ali',
'family': 'Ozturk',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-3086-0995',
'authenticated-orcid': False,
'given': 'Bashar',
'family': 'Ibrahim',
'sequence': 'additional',
'affiliation': []}],
'member': '297',
'published-online': {'date-parts': [[2022, 8, 24]]},
'reference': [ { 'key': '3400_CR1',
'doi-asserted-by': 'publisher',
'first-page': '1198',
'DOI': '10.7150/ijms.50039',
'volume': '18',
'author': 'Y Tu',
'year': '2021',
'unstructured': 'Tu Y, Yang P, Zhou Y, Wen X, Li Q, Zhou J et al (2021) Risk factors for '
'mortality of critically ill patients with covid-19 receiving invasive '
'ventilation. Int J Med Sci 18:1198–1206. '
'https://doi.org/10.7150/ijms.50039',
'journal-title': 'Int J Med Sci'},
{ 'issue': '3',
'key': '3400_CR2',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1177/2473974X20957975',
'volume': '4',
'author': 'TS Ibekwe',
'year': '2020',
'unstructured': 'Ibekwe TS, Fasunla AJ, Orimadegun AE (2020) Systematic review and '
'meta-analysis of smell and taste disorders in COVID-19. OTO Open '
'4(3):1–13. https://doi.org/10.1177/2473974X20957975',
'journal-title': 'OTO Open'},
{ 'key': '3400_CR3',
'doi-asserted-by': 'publisher',
'first-page': '104773',
'DOI': '10.1016/j.meegid.2021.104773',
'volume': '90',
'author': 'B Bakhshandeh',
'year': '2021',
'unstructured': 'Bakhshandeh B, Sorboni SG, Javanmard AR, Mottaghi SS, Mehrabi M, Sorouri '
'F et al (2021) Variants in ACE2; potential influences on virus infection '
'and COVID-19 severity. InInfect Genet Evol 90:104773. '
'https://doi.org/10.1016/j.meegid.2021.104773',
'journal-title': 'InInfect Genet Evol'},
{ 'issue': '3',
'key': '3400_CR4',
'doi-asserted-by': 'publisher',
'first-page': 'L301',
'DOI': '10.1152/AJPLUNG.00259.2020',
'volume': '320',
'author': 'G Pathangey',
'year': '2021',
'unstructured': 'Pathangey G, Fadadu PP, Hospodar AR, Abbas AE (2021) '
'Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, '
'and therapies. Am J Physiol Lung Cell Mol Physiol 320(3):L301–L330. '
'https://doi.org/10.1152/AJPLUNG.00259.2020',
'journal-title': 'Am J Physiol Lung Cell Mol Physiol'},
{ 'key': '3400_CR5',
'doi-asserted-by': 'publisher',
'first-page': '234',
'DOI': '10.1097/MRM.0000000000000217',
'volume': '31',
'author': 'A Ozturk',
'year': '2020',
'unstructured': 'Ozturk A, Abdulmajed O, Ibrahim B (2020) What is the novel coronavirus '
'disease 2019 (COVID-19) that paralyze the world? Rev Med Microbiol '
'31:234–241. https://doi.org/10.1097/MRM.0000000000000217',
'journal-title': 'Rev Med Microbiol'},
{ 'key': '3400_CR6',
'doi-asserted-by': 'publisher',
'first-page': '100741',
'DOI': '10.1016/j.jbior.2020.100741',
'volume': '77',
'author': 'G Schönrich',
'year': '2020',
'unstructured': 'Schönrich G, Raftery MJ, Samstag Y (2020) Devilishly radical NETwork in '
'COVID-19: oxidative stress, neutrophil extracellular traps (NETs), and T '
'cell suppression. Adv Biol Regul 77:100741. '
'https://doi.org/10.1016/j.jbior.2020.100741',
'journal-title': 'Adv Biol Regul'},
{ 'key': '3400_CR7',
'doi-asserted-by': 'publisher',
'first-page': '1324',
'DOI': '10.1111/jth.14859',
'volume': '18',
'author': 'L Zhang',
'year': '2020',
'unstructured': 'Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z et al (2020) D-dimer levels '
'on admission to predict in-hospital mortality in patients with Covid-19. '
'J Thromb Haemost 18:1324–1329. https://doi.org/10.1111/jth.14859',
'journal-title': 'J Thromb Haemost'},
{ 'issue': '6',
'key': '3400_CR8',
'doi-asserted-by': 'publisher',
'first-page': '644',
'DOI': '10.1007/s10930-020-09935-8',
'volume': '39',
'author': 'S Suhail',
'year': '2020',
'unstructured': 'Suhail S, Zajac J, Fossum C, Lowater H, McCracken C, Severson N et al '
'(2020) Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 '
'(COVID-19) ınfection: a review. Protein J 39(6):644–656. '
'https://doi.org/10.1007/s10930-020-09935-8',
'journal-title': 'Protein J'},
{ 'issue': '45',
'key': '3400_CR9',
'doi-asserted-by': 'publisher',
'first-page': 'e13087',
'DOI': '10.1097/MD.0000000000013087',
'volume': '97',
'author': 'Q Zhang',
'year': '2018',
'unstructured': 'Zhang Q, Ju Y, Ma Y, Wang T (2018) N-acetylcysteine improves oxidative '
'stress and inflammatory response in patients with community acquired '
'pneumonia. Medicine (Baltimore) 97(45):e13087. '
'https://doi.org/10.1097/MD.0000000000013087',
'journal-title': 'Medicine (Baltimore)'},
{ 'key': '3400_CR10',
'doi-asserted-by': 'publisher',
'first-page': '688',
'DOI': '10.1016/j.freeradbiomed.2021.06.018',
'volume': '172',
'author': 'N Saheb Sharif-Askari',
'year': '2021',
'unstructured': 'Saheb Sharif-Askari N, Saheb Sharif-Askari F, Mdkhana B, Hussain Alsayed '
'HA, Alsafar H, Alrais ZF et al (2021) Upregulation of oxidative stress '
'gene markers during SARS-COV-2 viral infection. Free Radical Biol Med '
'172:688–698. https://doi.org/10.1016/j.freeradbiomed.2021.06.018',
'journal-title': 'Free Radical Biol Med'},
{ 'key': '3400_CR11',
'doi-asserted-by': 'publisher',
'unstructured': 'Roche JV, Törnroth-Horsefield S (2017) Aquaporin protein-protein '
'interactions. Int J Mol 18:2255. https://doi.org/10.3390/ijms18112255',
'DOI': '10.3390/ijms18112255'},
{ 'issue': '8',
'key': '3400_CR12',
'doi-asserted-by': 'publisher',
'first-page': '1229',
'DOI': '10.3390/ijms17081229',
'volume': '17',
'author': 'M Wang',
'year': '2016',
'unstructured': 'Wang M, Ding L, Gao L, Li Y, Shen Q, Guo S (2016) The interactions of '
'aquaporins and mineral nutrients in higher plants. Int J Mol Sci '
'17(8):1229. https://doi.org/10.3390/ijms17081229',
'journal-title': 'Int J Mol Sci'},
{ 'key': '3400_CR13',
'doi-asserted-by': 'publisher',
'first-page': '110201',
'DOI': '10.1016/j.mehy.2020.110201',
'volume': '143',
'author': 'LF Mariajoseph-Antony',
'year': '2020',
'unstructured': 'Mariajoseph-Antony LF, Kannan A, Panneerselvam A, Loganathan C, Anbarasu '
'K, Prahalathan C (2020) Could aquaporin modulators be employed as '
'prospective drugs for COVID-19 related pulmonary comorbidity? Med '
'Hypotheses 143:110201. https://doi.org/10.1016/j.mehy.2020.110201',
'journal-title': 'Med Hypotheses'},
{ 'key': '3400_CR14',
'doi-asserted-by': 'publisher',
'first-page': '37597',
'DOI': '10.1074/jbc.M205305200',
'volume': '277',
'author': 'HN Hunter',
'year': '2002',
'unstructured': 'Hunter HN, Bruce Fulton D, Ganz T, Vogel HJ (2002) The solution '
'structure of human hepcidin, a peptide hormone with antimicrobial '
'activity that is involved in iron uptake and hereditary hemochromatosis. '
'J Biol Chem 277:37597–37603. https://doi.org/10.1074/jbc.M205305200',
'journal-title': 'J Biol Chem'},
{ 'issue': '7',
'key': '3400_CR15',
'doi-asserted-by': 'publisher',
'first-page': '2461',
'DOI': '10.1182/blood-2002-10',
'volume': '101',
'author': 'E Nemeth',
'year': '2003',
'unstructured': 'Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T '
'(2003) Hepcidin, a putative mediator of anemia of inflammation, is a '
'type II acute-phase protein. Blood 101(7):2461–3. '
'https://doi.org/10.1182/blood-2002-10',
'journal-title': 'Blood'},
{ 'issue': '8',
'key': '3400_CR16',
'doi-asserted-by': 'publisher',
'first-page': 'e1004998',
'DOI': '10.1371/journal.ppat.1004998',
'volume': '11',
'author': 'K Michels',
'year': '2015',
'unstructured': 'Michels K, Nemeth E, Ganz T, Mehrad B (2015) Hepcidin and host defense '
'against ınfectious diseases. PLoS Pathog 11(8):e1004998. '
'https://doi.org/10.1371/journal.ppat.1004998',
'journal-title': 'PLoS Pathog'},
{ 'key': '3400_CR17',
'doi-asserted-by': 'publisher',
'first-page': '417',
'DOI': '10.1152/ajplung.00484.2005.-Alveolar',
'volume': '291',
'author': 'NB Nguyen',
'year': '2006',
'unstructured': 'Nguyen NB, Callaghan KD, Ghio AJ, Haile DJ, Yang F, Hepcidin YF et al '
'(2006) Expression and iron transport in alveolar macrophages. Am J '
'Physiol Lung Cell Mol Physiol 291:417–425. '
'https://doi.org/10.1152/ajplung.00484.2005.-Alveolar',
'journal-title': 'Am J Physiol Lung Cell Mol Physiol'},
{ 'key': '3400_CR18',
'doi-asserted-by': 'publisher',
'unstructured': 'Ehsani S (2020) COVID-19 and iron dysregulation: distant sequence '
'similarity between hepcidin and the novel coronavirus spike '
'glycoprotein. Biol Direct 15(1):19. '
'https://doi.org/10.1186/s13062-020-00275-2',
'DOI': '10.1186/s13062-020-00275-2'},
{ 'issue': '12',
'key': '3400_CR19',
'doi-asserted-by': 'publisher',
'first-page': '1912',
'DOI': '10.1039/d0mt00220h',
'volume': '12',
'author': 'JR de Jesus',
'year': '2020',
'unstructured': 'de Jesus JR, de Araújo Andrade T (2020) Understanding the relationship '
'between viral infections and trace elements from a metallomics '
'perspective: ımplications for COVID-19. Metallomics 12(12):1912–1930. '
'https://doi.org/10.1039/d0mt00220h',
'journal-title': 'Metallomics'},
{ 'key': '3400_CR20',
'doi-asserted-by': 'publisher',
'first-page': '1148',
'DOI': '10.1056/nejmra1804281',
'volume': '381',
'author': 'T Ganz',
'year': '2019',
'unstructured': 'Ganz T (2019) Anemia of ınflammation. N Engl J Med 381:1148–1157. '
'https://doi.org/10.1056/nejmra1804281',
'journal-title': 'N Engl J Med'},
{ 'key': '3400_CR21',
'doi-asserted-by': 'publisher',
'first-page': '109',
'DOI': '10.1016/j.jtemb.2017.06.008',
'volume': '44',
'author': 'M Wacewicz',
'year': '2017',
'unstructured': 'Wacewicz M, Socha K, Soroczyńska J, Niczyporuk M, Aleksiejczuk P, '
'Ostrowska J et al (2017) 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 44:109–114. '
'https://doi.org/10.1016/j.jtemb.2017.06.008',
'journal-title': 'J Trace Elem Med Biol'},
{ 'issue': '4',
'key': '3400_CR22',
'doi-asserted-by': 'publisher',
'first-page': 'e00049',
'DOI': '10.1042/BSR20130014',
'volume': '33',
'author': 'SL Stafford',
'year': '2013',
'unstructured': 'Stafford SL, Bokil NJ, Achard MES, Kapetanovic R, Schembri MA, Mcewan AG '
'et al (2013) Metal ions in macrophage antimicrobial pathways: emerging '
'roles for zinc and copper. Biosci Rep 33(4):e00049. '
'https://doi.org/10.1042/BSR20130014',
'journal-title': 'Biosci Rep'},
{ 'key': '3400_CR23',
'doi-asserted-by': 'publisher',
'first-page': '109',
'DOI': '10.1016/j.nutres.2021.05.008',
'volume': '92',
'author': 'I Rani',
'year': '2021',
'unstructured': 'Rani I, Goyal A, Bhatnagar M, Manhas S, Goel P, Pal A et al (2021) '
'Potential molecular mechanisms of zinc- and copper-mediated antiviral '
'activity on COVID-19. Nutr Res 92:109–128. '
'https://doi.org/10.1016/j.nutres.2021.05.008',
'journal-title': 'Nutr Res'},
{ 'issue': '2',
'key': '3400_CR24',
'doi-asserted-by': 'publisher',
'first-page': '412',
'DOI': '10.1093/ajcn/62.2.412',
'volume': '62',
'author': 'DS Kelley',
'year': '1995',
'unstructured': 'Kelley DS, Daudu PA, Taylor PC, Mackey BE, Turniund JR (1995) Effects of '
'low-copper diets on human immune response. Am J Clin Nutr 62(2):412–416. '
'https://doi.org/10.1093/ajcn/62.2.412',
'journal-title': 'Am J Clin Nutr'},
{ 'key': '3400_CR25',
'doi-asserted-by': 'publisher',
'first-page': '109814',
'DOI': '10.1016/j.mehy.2020.109814',
'volume': '142',
'author': 'S Raha',
'year': '2020',
'unstructured': 'Raha S, Mallick R, Basak S, Duttaroy AK (2020) Is copper beneficial for '
'COVID-19 patients? Med Hypotheses 142:109814. '
'https://doi.org/10.1016/j.mehy.2020.109814',
'journal-title': 'Med Hypotheses'},
{ 'issue': '22',
'key': '3400_CR26',
'doi-asserted-by': 'publisher',
'first-page': '10840',
'DOI': '10.1021/acs.chemrev.8b00074',
'volume': '118',
'author': 'SM Adam',
'year': '2018',
'unstructured': 'Adam SM, Wijeratne GB, Rogler PJ, Diaz DE, Quist DA, Liu JJ et al (2018) '
'Synthetic Fe/Cu complexes: toward understanding heme-copper oxidase '
'structure and function. Chem Rev 118(22):10840–11022. '
'https://doi.org/10.1021/acs.chemrev.8b00074',
'journal-title': 'Chem Rev'},
{ 'issue': '9',
'key': '3400_CR27',
'doi-asserted-by': 'publisher',
'first-page': '689',
'DOI': '10.1038/s41573-021-00233-1',
'volume': '20',
'author': 'HJ Forman',
'year': '2021',
'unstructured': 'Forman HJ, Zhang H (2021) Targeting oxidative stress in disease: promise '
'and limitations of antioxidant therapy. Nat Rev Drug Discov '
'20(9):689–709. https://doi.org/10.1038/s41573-021-00233-1',
'journal-title': 'Nat Rev Drug Discov'},
{ 'key': '3400_CR28',
'doi-asserted-by': 'publisher',
'first-page': '1103',
'DOI': '10.1016/j.clinbiochem.2005.08.008',
'volume': '38',
'author': 'O Erel',
'year': '2005',
'unstructured': 'Erel O (2005) A new automated colorimetric method for measuring total '
'oxidant status. Clin Biochem 38:1103–1111. '
'https://doi.org/10.1016/j.clinbiochem.2005.08.008',
'journal-title': 'Clin Biochem'},
{ 'issue': '10',
'key': '3400_CR29',
'doi-asserted-by': 'publisher',
'first-page': '3198',
'DOI': '10.3390/nu12103198',
'volume': '12',
'author': 'F Pecora',
'year': '2020',
'unstructured': 'Pecora F, Persico F, Argentiero A, Neglia C, Esposito S (2020) The role '
'of micronutrients in support of the immune response against viral '
'infections. Nutrients 12(10):3198. https://doi.org/10.3390/nu12103198',
'journal-title': 'Nutrients'},
{ 'issue': '6 Pt 1',
'key': '3400_CR30',
'doi-asserted-by': 'publisher',
'first-page': '1309',
'DOI': '10.1093/clinchem/44.6.1309',
'volume': '44',
'author': 'G Cao',
'year': '1998',
'unstructured': 'Cao G, Prior RL (1998) Comparison of different analytical methods for '
'assessing total antioxidant capacity of human serum Automation and '
'Analytical Techniques. Clin Chem 44(6 Pt 1):1309–1315',
'journal-title': 'Clin Chem'},
{ 'issue': '6',
'key': '3400_CR31',
'doi-asserted-by': 'publisher',
'first-page': '971',
'DOI': '10.3390/antiox10060971',
'volume': '10',
'author': 'N Cárdenas-Rodríguez',
'year': '2021',
'unstructured': 'Cárdenas-Rodríguez N, Bandala C, Vanoye-Carlo A, Ignacio-Mejía I, '
'Gómez-Manzo S, Hernández-Cruz EY et al (2021) Use of antioxidants for '
'the neuro-therapeutic management of covid-19. Antioxidants (Basel) '
'10(6):971. https://doi.org/10.3390/antiox10060971',
'journal-title': 'Antioxidants (Basel)'},
{ 'key': '3400_CR32',
'doi-asserted-by': 'publisher',
'first-page': '111016',
'DOI': '10.1016/j.nut.2020.111016',
'volume': '81',
'author': 'D Fedele',
'year': '2021',
'unstructured': 'Fedele D, de Francesco A, Riso S, Collo A (2021) Obesity, malnutrition, '
'and trace element deficiency in the coronavirus disease (COVID-19) '
'pandemic: an overview. Nutrition 81:111016. '
'https://doi.org/10.1016/j.nut.2020.111016',
'journal-title': 'Nutrition'},
{ 'issue': '1',
'key': '3400_CR33',
'doi-asserted-by': 'publisher',
'first-page': 'E32',
'DOI': '10.1002/ajh.26027',
'volume': '96',
'author': 'A Nai',
'year': '2021',
'unstructured': 'Nai A, Lorè N, Pagani A, De Lorenzo R, Di Modica S, Saliu F et al (2021) '
'Hepcidin levels predict Covid19 severity and mortality in a cohort of '
'hospitalized Italian patients. Am J Hematol 96(1):E32–E35. '
'https://doi.org/10.1002/ajh.26027',
'journal-title': 'Am J Hematol'},
{ 'key': '3400_CR34',
'doi-asserted-by': 'publisher',
'first-page': '324',
'DOI': '10.1016/j.resp.2007.02.012',
'volume': '159',
'author': 'AS Verkman',
'year': '2007',
'unstructured': 'Verkman AS (2007) Role of aquaporins in lung liquid physiology. Respir '
'Physiol Neurobiol 159:324–330. '
'https://doi.org/10.1016/j.resp.2007.02.012',
'journal-title': 'Respir Physiol Neurobiol'},
{ 'key': '3400_CR35',
'doi-asserted-by': 'publisher',
'unstructured': 'Wittekindt OH, Dietl P (2019) Aquaporins in the lung, Pflugers Archiv '
'European. Pflugers Arch 471(4):519–532. '
'https://doi.org/10.1007/s00424-018-2232-y',
'DOI': '10.1007/s00424-018-2232-y'},
{ 'key': '3400_CR36',
'doi-asserted-by': 'publisher',
'first-page': '244',
'DOI': '10.3390/metabo11040244',
'volume': '11',
'author': 'AV Skalny',
'year': '2021',
'unstructured': 'Skalny AV, Timashev PS, Aschner M, Aaseth J, Chernova LN, Belyaev VE et '
'al (2021) Serum zinc, copper, and other biometals are associated with '
'COVID-19 severity markers. Metabolites 11:244. '
'https://doi.org/10.3390/metabo11040244',
'journal-title': 'Metabolites'}],
'container-title': 'Biological Trace Element Research',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s12011-022-03400-6.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/article/10.1007/s12011-022-03400-6/fulltext.html',
'content-type': 'text/html',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/content/pdf/10.1007/s12011-022-03400-6.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 8, 24]],
'date-time': '2022-08-24T09:51:38Z',
'timestamp': 1661334698000},
'score': 1,
'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s12011-022-03400-6'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 8, 24]]},
'references-count': 36,
'alternative-id': ['3400'],
'URL': 'http://dx.doi.org/10.1007/s12011-022-03400-6',
'relation': {},
'ISSN': ['0163-4984', '1559-0720'],
'subject': [ 'Biochemistry (medical)', 'Inorganic Chemistry', 'Clinical Biochemistry', 'General Medicine',
'Biochemistry', 'Endocrinology, Diabetes and Metabolism'],
'container-title-short': 'Biol Trace Elem Res',
'published': {'date-parts': [[2022, 8, 24]]},
'assertion': [ { 'value': '23 May 2022',
'order': 1,
'name': 'received',
'label': 'Received',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '18 August 2022',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '24 August 2022',
'order': 3,
'name': 'first_online',
'label': 'First Online',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}},
{ 'value': 'This study was approved by the local ethics committee of Harran University and '
'the Ministry of Health of Turkey (18/01/2020-HRU/210231).',
'order': 2,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Ethics Approval'}},
{ 'value': 'All patients signed an informed consent for inclusion of personal records in '
'the local database and for use to scientifc research purposes.',
'order': 3,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Consent to Participate'}},
{ 'value': 'Not applicable.',
'order': 4,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Consent for Publication'}},
{ 'value': 'The authors declare no competing interests.',
'order': 5,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Conflict of Interest'}},
{ 'value': 'This content has been made available to all.',
'name': 'free',
'label': 'Free to read'}]}
