{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:13:21Z","timestamp":1778163201793,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Doxorubicin is an antineoplastic drug used to treat cancer. However, side effects limit its use. Edaravone (EDO) is a recently discovered, powerful drug with antioxidant properties. The aim of the present study was to show the negative effects of doxorubicin and the protective effect of EDO on the thyroid gland using scintigraphic and biochemical methods. Materials and Methods: Thirty-five male Wistar rats were randomly divided into five groups (n = 7) to establish the following study groups: control, doxorubicin, and 1, 10, or 30 mg\/kg EDO. DOX (18 mg\/kg cumulative intraperitoneal injection (i.p.) was performed on the 19th, 20th, and 21st days of the experiment. EDO (1, 10, and 30 mg\/kg) was administered on the first day of the trial and continued for 21 days. These groups also received i.p. injections of DOX (18 mg\/kg) on the 19th, 20th, and 21st days of the experiment. On the 22nd day of the experiment, scintigraphic imaging of the thyroid glands of rats was performed using 99mTc pertechnetate as the radiopharmaceutical. Serum levels of T3, T4, TSH, NLRP3, IL-1\u03b2, and IL-18, as well as thyroid tissue levels of MDA, TNF-\u03b1, and IL-6, were determined using the ELISA method. Results: DOX significantly reduced 99mTc pertechnetate uptake in the thyroid gland compared to the control group (p &lt; 0.001). It reduced plasma levels of thyroid hormones T3 (p &lt; 0.001) and T4 (p &lt; 0.001) while increasing TSH levels (p &lt; 0.01). Additionally, NLRP3, IL-1\u03b2, IL-18, MDA, TNF-\u03b1, and IL-6 levels were significantly increased in the DOX group compared with the control group (all p &lt; 0.001). Pretreatment with EDO significantly attenuated doxorubicin-induced abnormalities in the thyroid gland (p &lt; 0.001). Conclusions: The data from scintigraphic and biochemical analyses revealed the development of hypothyroidism after doxorubicin administration in rats. It was shown that pretreatment with EDO could partially prevent hypothyroidism caused by doxorubicin.<\/jats:p>","DOI":"10.3390\/medicina62050894","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:15:07Z","timestamp":1778156107000},"page":"894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effect of Edaravone on Doxorubicin-Induced Thyroid Dysfunction in Rats Revealed by 99mTc Pertechnetate Thyroid Gland Scintigraphy and Biochemical Methods"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-9413","authenticated-orcid":false,"given":"Murat","family":"Kal\u0131n","sequence":"first","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-0562","authenticated-orcid":false,"given":"Hatice","family":"Aygun","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory, Biruni University Research Center (BAMER), Biruni University, Istanbul 34010, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-8297","authenticated-orcid":false,"given":"Haluk Kerim","family":"Karakullukcu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8174-5471","authenticated-orcid":false,"given":"Mina","family":"Karakullukcu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4049-644X","authenticated-orcid":false,"given":"Aylin","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Istanbul Prof. Dr. Cemil Ta\u015f\u00e7\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4822-2588","authenticated-orcid":false,"given":"Serdar Savas","family":"Gul","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine, Lokman Hekim University, Ankara 06530, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6644-2413","authenticated-orcid":false,"given":"\u00d6mer Faruk","family":"\u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-9298","authenticated-orcid":false,"given":"G\u00fcl\u00e7in","family":"Ercan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.jprot.2011.02.013","article-title":"Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte","volume":"74","author":"Kumar","year":"2011","journal-title":"J. Proteom."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/tcm.1016","article-title":"Teratogenic effects of doxorubicin in rats at midgestation and at term","volume":"21","author":"Menegola","year":"2001","journal-title":"Teratog. Carcinog. Mutagen."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.2174\/092986709788803312","article-title":"Doxorubicin: The good, the bad and the ugly effect","volume":"16","author":"Carvalho","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4103\/mj.mj_43_23","article-title":"Thyroid Gland Basics: A Comprehensive Review","volume":"22","author":"Assi","year":"2023","journal-title":"Mustansiriya Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1152\/physrev.00030.2013","article-title":"Thyroid hormone regulation of metabolism","volume":"94","author":"Mullur","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1136\/adc.64.4.593","article-title":"Thyroid dysfunction after radiotherapy and chemotherapy of brain tumours","volume":"64","author":"Livesey","year":"1989","journal-title":"Arch. Dis. Child."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.ijrobp.2008.11.037","article-title":"Thyroid function in women after multimodal treatment for breast cancer stage II\/III: Comparison with controls from a population sample","volume":"75","author":"Reinertsen","year":"2009","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1080\/0284186X.2021.1958004","article-title":"Thyroid hypofunction in aging testicular cancer survivors","volume":"60","author":"Nome","year":"2021","journal-title":"Acta Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115245","DOI":"10.1016\/j.biopha.2023.115245","article-title":"Comparative evaluation of doxorubicin, cyclophosphamide, 5-fluorouracil, and cisplatin on cognitive dysfunction in rats: Delineating the role of inflammation of hippocampal neurons and hypothyroidism","volume":"165","author":"Alotayk","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","first-page":"9388","article-title":"Pioglitazone ameliorates doxorubicin-induced hypothyroidism and cardiotoxicity in rat models","volume":"27","author":"Alhowail","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"542","DOI":"10.3923\/ijp.2023.542.547","article-title":"Ameliorative effect of galantamine on doxorubicin-induced cardiotoxicity and hypothyroidism","volume":"19","author":"Aldubayan","year":"2023","journal-title":"Int. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1159\/000069318","article-title":"Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebocontrolled, double-blind study at multicenters","volume":"15","author":"Franke","year":"2003","journal-title":"Cerebrovasc. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jss.2018.03.020","article-title":"Dose-dependency of multiple free radicalscavenging activity of edaravone","volume":"228","author":"Tokumaru","year":"2018","journal-title":"J. Surg. Res."},{"key":"ref_14","first-page":"10","article-title":"Protective effect of edaravone on adriamycin-induced cardiotoxicity in rats","volume":"41","year":"2019","journal-title":"Cumhur. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0014-2999(02)02251-3","article-title":"Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats","volume":"451","author":"Sueishi","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.ijporl.2013.04.003","article-title":"Protective effects of edaravone against cisplatin-induced hair cell damage in zebrafish","volume":"77","author":"Hong","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.heares.2015.08.004","article-title":"Protective role of edaravone against cisplatin-induced ototoxicity in an auditory cell line","volume":"330","author":"Im","year":"2015","journal-title":"Hear. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105967","DOI":"10.1016\/j.intimp.2019.105967","article-title":"Potential use of edaravone to reduce specific side effects of chemo-, radio- and immuno-therapy of cancers","volume":"77","author":"Bailly","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","first-page":"2037","article-title":"Edaravone ameliorates experimental autoimmune thyroiditis in rats through HO-1-dependent STAT3\/PI3K\/Akt pathway","volume":"10","author":"Li","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110428","DOI":"10.1016\/j.cbi.2023.110428","article-title":"Cadmium-promoted thyroid hormones disruption mediates ROS, inflammation, A\u03b2 and Tau proteins production, gliosis, spongiosis and neurodegeneration in rat basal forebrain","volume":"375","author":"Sola","year":"2023","journal-title":"Chem.-Biol. Interact."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3769\/radioisotopes.38.8_344","article-title":"Evaluation of thyroid scintigraphy in small animals","volume":"38","author":"Kaneko","year":"1989","journal-title":"Radioisotopes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1053\/j.semnuclmed.2013.08.007","article-title":"Thyroid scintigraphy in veterinary medicine","volume":"44","author":"Daniel","year":"2014","journal-title":"Semin. Nucl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1007\/s00210-019-01683-6","article-title":"Beneficial effects of edaravone in experimental model of amitriptyline-induced cardiotoxicity in rats","volume":"392","author":"Basol","year":"2019","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/fcp.12651","article-title":"Anticonvulsive effects of edaravone on penicillin-induced focal onset seizure model in the conscious rats","volume":"35","author":"Kurt","year":"2021","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_25","first-page":"861","article-title":"Radioprotective effect of thymol against salivary glands dysfunction induced by ionizing radiation in rats","volume":"15","author":"Abedi","year":"2016","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109206","DOI":"10.1016\/j.radphyschem.2020.109206","article-title":"The role of melatonin on acute thyroid damage induced by high dose rate X-ray in head and neck radiotherapy","volume":"179","author":"Aras","year":"2021","journal-title":"Radiat. Phys. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.archoralbio.2015.06.003","article-title":"Vitamin E protects salivary glands dysfunction induced by ionizing radiation in rats","volume":"60","author":"Abedi","year":"2015","journal-title":"Arch. Oral Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/jmri.21026","article-title":"Automated analysis of contrast enhancement in breast MRI lesions using mean shift clustering for ROI selection","volume":"26","author":"Stoutjesdijk","year":"2007","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/mpo.2950090505","article-title":"Cyclical combination chemotherapy and thyroid function in patients with advanced Hodgkins disease","volume":"9","author":"Sutcliffe","year":"1981","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rand, J. (2013). Hypothyroidism in dogs. Clinical Endocrinology of Companion Animals, John Wiley & Sons, Inc.","DOI":"10.1002\/9781118997093"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ijdevneu.2012.11.005","article-title":"Gestational doxorubicin alters fetal thyroid\u2013brain axis","volume":"31","author":"Ahmed","year":"2013","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_32","first-page":"516","article-title":"Clinical application of thyroidal I-131 uptake test in the dog","volume":"135","author":"Kaneko","year":"1959","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1007\/s12149-014-0909-7","article-title":"Comparison of radioactive iodide uptake in the rat thyroid between oral and intravenous bolus administration","volume":"28","author":"Kurosawa","year":"2014","journal-title":"Ann. Nucl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1740-8261.1985.tb01113.x","article-title":"The normal feline thyroid: Technetium pertechnetate imaging and determination of thyroid to salivary gland radioactivity ratios in 10 normal cats","volume":"26","author":"Beck","year":"1985","journal-title":"Vet. Radiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1007\/s00018-020-03729-y","article-title":"Molecular mechanisms of doxorubicin-induced cardiotoxicity: Novel roles of sirtuin 1-mediated signaling pathways","volume":"78","author":"Wang","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, X., Tian, C., Zhang, Z., Qin, Y., Meng, R., Dai, X., Zhong, Y., Wei, X., Zhang, J., and Shen, C. (2023). Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2\/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction. Front. Biosci. (Landmark Ed.), 28.","DOI":"10.31083\/j.fbl2803045"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Singla, D.K., Johnson, T.A., and Tavakoli Dargani, Z. (2019). Exosome Treatment Enhances Anti-Inflammatory M2 Macrophages and Reduces Inflammation-Induced Pyroptosis in Doxorubicin-Induced Cardiomyopathy. Cells, 8.","DOI":"10.3390\/cells8101224"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111708","DOI":"10.1016\/j.biopha.2021.111708","article-title":"Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management","volume":"139","author":"Rawat","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gad, N.S., Shabana, S.M., Amer, M.E., Othman, A.I., and El-Missiry, M.A. (2025). Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect. BMC Pharmacol. Toxicol., 26.","DOI":"10.1186\/s40360-025-00947-7"},{"key":"ref_40","first-page":"4718","article-title":"Pregnenolone protects the liver against doxorubicin-induced cellular injury by anti-inflammatory, antioxidant, and antiapoptotic mechanisms: Role of Keap1\/Nrf2\/HO-1 and P-glycoprotein","volume":"27","author":"Morsy","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.4161\/cbt.11.12.15540","article-title":"Doxorubicin and daunorubicin induce processing and release of interleukin-1\u03b2 through activation of the NLRP3 inflammasome","volume":"11","author":"Sauter","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e70066","DOI":"10.1002\/prp2.70066","article-title":"Edaravone is a Therapeutic Candidate for Doxorubicin-Induced Cardiomyopathy by Activating the Nrf2 Pathway","volume":"13","author":"Yoshikawa","year":"2025","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s11033-025-10343-3","article-title":"Edaravone reduces brain injury in hepatic encephalopathy by upregulation of Nrf2\/HO-1 and inhibition of NF-\u03baB, iNOS\/NO and inflammatory cytokines","volume":"52","author":"Amirshahrokhi","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104468","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104468","article-title":"Edaravone administration confers neuroprotection after experimental intracerebral hemorrhage in rats via NLRP3 suppression","volume":"29","author":"Miao","year":"2020","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, J., Dai, X., Zhou, L., Li, X., and Pan, D. (2021). Edaravone Plays Protective Effects on LPS-Induced Microglia by Switching M1\/M2 Phenotypes and Regulating NLRP3 Inflammasome Activation. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.691773"},{"key":"ref_46","first-page":"101","article-title":"The novel antioxidant edaravone: From bench to bedside","volume":"26","author":"Watanabe","year":"2008","journal-title":"Cardiovasc. Cardiovasc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3109\/21678421.2014.959024","article-title":"Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients","volume":"15","author":"Abe","year":"2014","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41586-019-1291-3","article-title":"Mapping human microbiome drug metabolism by gut bacteria and their genes","volume":"570","author":"Zimmermann","year":"2019","journal-title":"Nature"},{"key":"ref_49","first-page":"189","article-title":"Thyroid dysfunction following conventional anthracycline-and taxane-based chemotherapy for breast cancer","volume":"1","author":"Kiyomatsu","year":"2022","journal-title":"Dokkyo Med. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1253\/circj.71.1815","article-title":"Edaravone, a potent free radical scavenger, prevents anthracycline-induced myocardial cell death","volume":"71","author":"Ikegami","year":"2007","journal-title":"Circ. J."},{"key":"ref_51","first-page":"177","article-title":"Cardioprotective effects of 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), a novel free radical scavenger, on acute autoimmune myocarditis in rats","volume":"9","author":"Okabe","year":"2004","journal-title":"Exp. Clin. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"333","DOI":"10.4196\/kjpp.2016.20.4.333","article-title":"Effect of edaravone in diabetes mellitus-induced nephropathy in rats","volume":"20","author":"Varatharajan","year":"2016","journal-title":"Korean J. Physiol. Pharmacol. Off. J. Korean Physiol. Soc. Korean Soc. Pharmacol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/894\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:35:08Z","timestamp":1778160908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["medicina62050894"],"URL":"https:\/\/doi.org\/10.3390\/medicina62050894","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]}}}