Evaluation of the cardiopulmonary effects of repurposed COVID-19 therapeutics in healthy rats

DOI record: { "DOI": "10.1038/s41598-025-31048-4", "ISSN": [ "2045-2322" ], "URL": "http://dx.doi.org/10.1038/s41598-025-31048-4", "alternative-id": [ "31048" ], "article-number": "1770", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "20 March 2025" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "28 November 2025" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "14 January 2026" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "The authors declare no competing interests." }, { "group": { "label": "Ethics approval", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "An application was made to Inonu University Faculty of Medicine Animal Experiments Local Ethics Committee for ethical approval and ethics committee permission was obtained at the meeting dated 06.01.2022 with ethical approval number 2021/1–6." } ], "author": [ { "ORCID": "https://orcid.org/0000-0001-9018-7849", "affiliation": [], "authenticated-orcid": false, "family": "Ozhan", "given": "Onural", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0001-5686-7867", "affiliation": [], "authenticated-orcid": false, "family": "Yildiz", "given": "Azibe", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-7793-1119", "affiliation": [], "authenticated-orcid": false, "family": "Bakar", "given": "Busra", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-4447-6233", "affiliation": [], "authenticated-orcid": false, "family": "Ulu", "given": "Ahmet", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-7956-9272", "affiliation": [], "authenticated-orcid": false, "family": "Kucukakcali", "given": "Zeynep", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-1723-2556", "affiliation": [], "authenticated-orcid": false, "family": "Karaca", "given": "Elif", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-0576-1696", "affiliation": [], "authenticated-orcid": false, "family": "Vardi", "given": "Nigar", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-6080-229X", "affiliation": [], "authenticated-orcid": false, "family": "Ates", "given": "Burhan", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-9497-3468", "affiliation": [], "authenticated-orcid": false, "family": "Parlakpinar", "given": "Hakan", "sequence": "additional" } ], "container-title": "Scientific Reports", "container-title-short": "Sci Rep", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T06:44:41Z", "timestamp": 1768373081000 }, "deposited": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T12:58:28Z", "timestamp": 1768395508000 }, "funder": [ { "DOI": "10.13039/100031253", "award": [ "TOA-2020-2347" ], "award-info": [ { "award-number": [ "TOA-2020-2347" ] } ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100031253", "id-type": "DOI" } ], "name": "İnönü Üniversitesi" } ], "indexed": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T23:24:26Z", "timestamp": 1768433066923, "version": "3.49.0" }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2026, 1, 14 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2026, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by-nc-nd/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T00:00:00Z", "timestamp": 1768348800000 } }, { "URL": "https://creativecommons.org/licenses/by-nc-nd/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T00:00:00Z", "timestamp": 1768348800000 } } ], "link": [ { "URL": "https://www.nature.com/articles/s41598-025-31048-4", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s41598-025-31048-4.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s41598-025-31048-4.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1038", "published": { "date-parts": [ [ 2026, 1, 14 ] ] }, "published-online": { "date-parts": [ [ 2026, 1, 14 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1016/j.gendis.2020.06.004", "author": "AH Al-Rohaimi", "doi-asserted-by": "publisher", "first-page": "491", "journal-title": "Genes Dis.", "key": "31048_CR1", "unstructured": "Al-Rohaimi, A. H., Al Otaibi, F. & Novel SARS-CoV-2 outbreak and COVID19 disease; a systemic review on the global pandemic. Genes Dis. 7, 491–501. https://doi.org/10.1016/j.gendis.2020.06.004 (2020).", "volume": "7", "year": "2020" }, { "DOI": "10.1038/s41586-020-2012-7", "author": "P Zhou", "doi-asserted-by": "publisher", "first-page": "270", "journal-title": "Nature", "key": "31048_CR2", "unstructured": "Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable Bat origin. Nature 579, 270–273. https://doi.org/10.1038/s41586-020-2012-7 (2020).", "volume": "579", "year": "2020" }, { "DOI": "10.1016/j.mayocp.2020.04.027", "author": "P Vijayvargiya", "doi-asserted-by": "publisher", "first-page": "1454", "journal-title": "Mayo Clin. Proc.", "key": "31048_CR3", "unstructured": "Vijayvargiya, P. et al. Treatment considerations for COVID-19: A critical review of the evidence (or lack Thereof). Mayo Clin. Proc. 95, 1454–1466. https://doi.org/10.1016/j.mayocp.2020.04.027 (2020).", "volume": "95", "year": "2020" }, { "DOI": "10.3389/fimmu.2022.855496", "doi-asserted-by": "publisher", "key": "31048_CR4", "unstructured": "Tian, L. et al. Molnupiravir and Its Antiviral Activity Against COVID-19. Front. Immunol. 13, https://doi.org/10.3389/fimmu.2022.855496 (2022)." }, { "DOI": "10.1002/14651858.CD015219.pub2", "doi-asserted-by": "publisher", "key": "31048_CR5", "unstructured": "Korula, P. et al. Favipiravir for treating COVID-19. The Cochrane database of systematic reviews 2, Cd015219, (2024). https://doi.org/10.1002/14651858.CD015219.pub2" }, { "DOI": "10.1186/s40360-023-00666-x", "doi-asserted-by": "publisher", "key": "31048_CR6", "unstructured": "Seydi, E., Hassani, M. K., Naderpour, S., Arjmand, A. & Pourahmad, J. Cardiotoxicity of chloroquine and hydroxychloroquine through mitochondrial pathway. BMC Pharmacol. Toxicol. 24, https://doi.org/10.1186/s40360-023-00666-x (2023)." }, { "DOI": "10.1080/14787210.2020.1799785", "author": "M Infante", "doi-asserted-by": "publisher", "first-page": "5", "journal-title": "Expert Rev. anti-infective Therapy", "key": "31048_CR7", "unstructured": "Infante, M., Ricordi, C., Alejandro, R., Caprio, M. & Fabbri, A. Hydroxychloroquine in the COVID-19 pandemic era: in pursuit of a rational use for prophylaxis of SARS-CoV-2 infection. Expert Rev. anti-infective Therapy. 19, 5–16. https://doi.org/10.1080/14787210.2020.1799785 (2021).", "volume": "19", "year": "2021" }, { "DOI": "10.1093/jac/dkaa114", "author": "D Zhou", "doi-asserted-by": "publisher", "first-page": "1667", "journal-title": "J. Antimicrob. Chemother.", "key": "31048_CR8", "unstructured": "Zhou, D., Dai, S. M. & Tong, Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J. Antimicrob. Chemother. 75, 1667–1670. https://doi.org/10.1093/jac/dkaa114 (2020).", "volume": "75", "year": "2020" }, { "DOI": "10.1093/cid/ciaa237", "author": "X Yao", "doi-asserted-by": "publisher", "first-page": "732", "journal-title": "Clin. Infect. Diseases: Official Publication Infect. Dis. Soc. Am.", "key": "31048_CR9", "unstructured": "Yao, X. et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin. Infect. Diseases: Official Publication Infect. Dis. Soc. Am. 71, 732–739. https://doi.org/10.1093/cid/ciaa237 (2020).", "volume": "71", "year": "2020" }, { "DOI": "10.2183/pjab.93.027", "author": "Y Furuta", "doi-asserted-by": "publisher", "first-page": "449", "journal-title": "Proc. Jpn. Acad. B", "key": "31048_CR10", "unstructured": "Furuta, Y., Komeno, T. & Nakamura, T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad. B. 93, 449–463. https://doi.org/10.2183/pjab.93.027 (2017).", "volume": "93", "year": "2017" }, { "DOI": "10.1016/j.ijid.2020.10.069", "author": "S Joshi", "doi-asserted-by": "publisher", "first-page": "501", "journal-title": "Int. J. Infect. Dis.", "key": "31048_CR11", "unstructured": "Joshi, S. et al. Role of favipiravir in the treatment of COVID-19. Int. J. Infect. Dis. 102, 501–508. https://doi.org/10.1016/j.ijid.2020.10.069 (2021).", "volume": "102", "year": "2021" }, { "DOI": "10.1016/j.ejmech.2023.115292", "author": "MS Bekheit", "doi-asserted-by": "publisher", "first-page": "115292", "journal-title": "Eur. J. Med. Chem.", "key": "31048_CR12", "unstructured": "Bekheit, M. S., Panda, S. S. & Girgis, A. S. Potential RNA-dependent RNA polymerase (RdRp) inhibitors as prospective drug candidates for SARS-CoV-2. Eur. J. Med. Chem. 252, 115292. https://doi.org/10.1016/j.ejmech.2023.115292 (2023).", "volume": "252", "year": "2023" }, { "DOI": "10.1126/scitranslmed.abl7430", "doi-asserted-by": "publisher", "key": "31048_CR13", "unstructured": "Fischer, W. A. et al. A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus. Science translational medicine 14, eabl7430, (2022). https://doi.org/10.1126/scitranslmed.abl7430" }, { "DOI": "10.1016/j.fct.2020.111887", "author": "S Thakur", "doi-asserted-by": "publisher", "first-page": "111887", "journal-title": "Food Chem. Toxicology: Int. J. Published Br. Industrial Biol. Res. Association", "key": "31048_CR14", "unstructured": "Thakur, S. et al. Exploring the magic bullets to identify achilles’ heel in SARS-CoV-2: delving deeper into the sea of possible therapeutic options in Covid-19 disease: an update. Food Chem. Toxicology. 147, 111887. https://doi.org/10.1016/j.fct.2020.111887 (2021).", "volume": "147", "year": "2021" }, { "DOI": "10.1016/j.ijantimicag.2020.106101", "author": "MS Khuroo", "doi-asserted-by": "publisher", "first-page": "106101", "journal-title": "Int. J. Antimicrob. Agents", "key": "31048_CR15", "unstructured": "Khuroo, M. S. Chloroquine and hydroxychloroquine in coronavirus disease 2019 (COVID-19). Facts, fiction and the hype: a critical appraisal. Int. J. Antimicrob. Agents. 56, 106101. https://doi.org/10.1016/j.ijantimicag.2020.106101 (2020).", "volume": "56", "year": "2020" }, { "DOI": "10.1007/s40121-021-00500-z", "author": "F Chen", "doi-asserted-by": "publisher", "first-page": "1907", "journal-title": "Infect. Dis. Therapy", "key": "31048_CR16", "unstructured": "Chen, F. et al. Potential adverse effects of dexamethasone therapy on COVID-19 patients: review and recommendations. Infect. Dis. Therapy. 10, 1907–1931. https://doi.org/10.1007/s40121-021-00500-z (2021).", "volume": "10", "year": "2021" }, { "DOI": "10.1007/s42399-020-00610-8", "author": "MH Ahmed", "doi-asserted-by": "publisher", "first-page": "2637", "journal-title": "SN Compr. Clin. Med.", "key": "31048_CR17", "unstructured": "Ahmed, M. H. & Hassan, A. Dexamethasone for the treatment of coronavirus disease (COVID-19): a review. SN Compr. Clin. Med. 2, 2637–2646. https://doi.org/10.1007/s42399-020-00610-8 (2020).", "volume": "2", "year": "2020" }, { "DOI": "10.1056/NEJMoa2021436", "author": "P Horby", "doi-asserted-by": "publisher", "first-page": "693", "journal-title": "N. Engl. J. Med.", "key": "31048_CR18", "unstructured": "Horby, P. et al. Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 384, 693–704. https://doi.org/10.1056/NEJMoa2021436 (2021).", "volume": "384", "year": "2021" }, { "DOI": "10.7247/jiumf.19.2.14", "doi-asserted-by": "crossref", "key": "31048_CR19", "unstructured": "Çolak, C. & Parlakpınar, H. Hayvan deneyleri: in vivo denemelerin bildirimi: ARRIVE Kılavuzu-Derleme. J. Turgut Ozal Med. Cent. 19, 128–131 https://doi.org/10.7247/jiumf.19.2.14 (2012)." }, { "DOI": "10.4103/0976-0105.177703", "author": "AB Nair", "doi-asserted-by": "publisher", "first-page": "27", "journal-title": "J. basic. Clin. Pharm.", "key": "31048_CR20", "unstructured": "Nair, A. B. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. basic. Clin. Pharm. 7, 27–31. https://doi.org/10.4103/0976-0105.177703 (2016).", "volume": "7", "year": "2016" }, { "DOI": "10.1111/fcp.12599", "author": "O Ozhan", "doi-asserted-by": "publisher", "first-page": "669", "journal-title": "Fundam. Clin. Pharmacol.", "key": "31048_CR21", "unstructured": "Ozhan, O., Parlakpinar, H. & Acet, A. Comparison of the effects of losartan, captopril, angiotensin II type 2 receptor agonist compound 21, and MAS receptor agonist AVE 0991 on myocardial ischemia-reperfusion necrosis in rats. Fundam. Clin. Pharmacol. 35, 669–680. https://doi.org/10.1111/fcp.12599 (2021).", "volume": "35", "year": "2021" }, { "DOI": "10.1007/s11419-025-00720-9", "author": "O Ozhan", "doi-asserted-by": "publisher", "first-page": "266", "journal-title": "Forensic Toxicol.", "key": "31048_CR22", "unstructured": "Ozhan, O. et al. Acute and subacute cardiovascular effects of synthetic cannabinoid JWH-018 in rat. Forensic Toxicol. 43, 266–279. https://doi.org/10.1007/s11419-025-00720-9 (2025).", "volume": "43", "year": "2025" }, { "DOI": "10.1093/cvr/22.7.447", "author": "MJ Walker", "doi-asserted-by": "publisher", "first-page": "447", "journal-title": "Cardiovascular. Res.", "key": "31048_CR23", "unstructured": "Walker, M. J. et al. The Lambeth conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion. Cardiovascular. Res. 22, 447–455. https://doi.org/10.1093/cvr/22.7.447 (1988).", "volume": "22", "year": "1988" }, { "DOI": "10.5455/annalsmedres.2023.08.180", "doi-asserted-by": "crossref", "key": "31048_CR24", "unstructured": "Yildiz, A. et al. Effects of drugs commonly used in Sars-CoV-2 infection on renal tissue in rats. Ann. Med. Res. 30, 1209-1216. https://doi.org/10.5455/annalsmedres.2023.08.180 (2023)." }, { "DOI": "10.1016/0003-2697(76)90527-3", "author": "MM Bradford", "doi-asserted-by": "publisher", "first-page": "248", "journal-title": "Anal. Biochem.", "key": "31048_CR25", "unstructured": "Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254. https://doi.org/10.1016/0003-2697(76)90527-3 (1976).", "volume": "72", "year": "1976" }, { "DOI": "10.1136/bmjresp-2020-000623", "doi-asserted-by": "publisher", "key": "31048_CR26", "unstructured": "Li, Z., Paulin, D., Lacolley, P., Coletti, D. & Agbulut, O. Vimentin as a target for the treatment of COVID-19. BMJ open. respiratory Res. 7, https://doi.org/10.1136/bmjresp-2020-000623 (2020)." }, { "DOI": "10.1128/mBio.02542-21", "doi-asserted-by": "publisher", "key": "31048_CR27", "unstructured": "Li, Z. et al. A Vimentin-Targeting Oral Compound with Host-Directed Antiviral and Anti-Inflammatory Actions Addresses Multiple Features of COVID-19 and Related Diseases. mBio. 12, e0254221, (2021). https://doi.org/10.1128/mBio.02542-21" }, { "DOI": "10.1038/s41598-024-72192-7", "author": "E Yilmaz", "doi-asserted-by": "publisher", "first-page": "29256", "journal-title": "Sci. Rep.", "key": "31048_CR28", "unstructured": "Yilmaz, E., Yilmaz, D. & Cacan, E. Severe and post-COVID-19 are associated with high expression of vimentin and reduced expression of N-cadherin. Sci. Rep. 14, 29256. https://doi.org/10.1038/s41598-024-72192-7 (2024).", "volume": "14", "year": "2024" }, { "DOI": "10.1165/rcmb.2022-0039LE", "author": "K Ruskowski", "doi-asserted-by": "publisher", "first-page": "405", "journal-title": "Am. J. Respir. Cell Mol. Biol.", "key": "31048_CR29", "unstructured": "Ruskowski, K. et al. Persistently elevated plasma concentrations of RIPK3, MLKL, HMGB1, and RIPK1 in patients with COVID-19 in the intensive care unit. Am. J. Respir. Cell Mol. Biol. 67, 405–408. https://doi.org/10.1165/rcmb.2022-0039LE (2022).", "volume": "67", "year": "2022" }, { "DOI": "10.1016/j.genrep.2022.101497", "author": "S Karabulut Uzuncakmak", "doi-asserted-by": "publisher", "first-page": "101497", "journal-title": "Gene Rep.", "key": "31048_CR30", "unstructured": "Karabulut Uzuncakmak, S., Dirican, E., Naldan, M. E., Kesmez Can, F. & Halıcı, Z. Investigation of CYP2E1 and Caspase-3 gene expressions in COVID-19 patients. Gene Rep. 26, 101497. https://doi.org/10.1016/j.genrep.2022.101497 (2022).", "volume": "26", "year": "2022" }, { "DOI": "10.1016/j.xagr.2023.100234", "author": "MA Bachnas", "doi-asserted-by": "publisher", "first-page": "100234", "journal-title": "AJOG Global Rep.", "key": "31048_CR31", "unstructured": "Bachnas, M. A. et al. Placental damage comparison between preeclampsia with COVID-19, COVID-19, and preeclampsia: analysis of caspase-3, caspase-1, and TNF-alpha expression. AJOG Global Rep. 3, 100234. https://doi.org/10.1016/j.xagr.2023.100234 (2023).", "volume": "3", "year": "2023" }, { "DOI": "10.22088/cjim.13.0.264", "author": "M Ramezani", "doi-asserted-by": "publisher", "first-page": "264", "journal-title": "Caspian J. Intern. Med.", "key": "31048_CR32", "unstructured": "Ramezani, M. et al. Altered serum and cerebrospinal fluid TNF-α, caspase 3, and IL 1β in COVID-19 disease. Caspian J. Intern. Med. 13, 264–269. https://doi.org/10.22088/cjim.13.0.264 (2022).", "volume": "13", "year": "2022" }, { "DOI": "10.1186/s40249-023-01086-z", "doi-asserted-by": "publisher", "key": "31048_CR33", "unstructured": "Yin, J. X. et al. Increased interleukin-6 is associated with long COVID-19: a systematic review and meta-analysis. Infect. Dis. poverty. 12, https://doi.org/10.1186/s40249-023-01086-z (2023)." }, { "DOI": "10.1089/jir.2022.0185", "author": "M Ghofrani Nezhad", "doi-asserted-by": "publisher", "first-page": "147", "journal-title": "J. Interferon Cytokine Research: Official J. Int. Soc. Interferon Cytokine Res.", "key": "31048_CR34", "unstructured": "Ghofrani Nezhad, M., Jami, G., Kooshkaki, O., Chamani, S. & Naghizadeh, A. The role of inflammatory cytokines (Interleukin-1 and Interleukin-6) as a potential biomarker in the different stages of COVID-19 (Mild, Severe, and Critical). J. Int. Soc. Interferon Cytokine Res. 43, 147–163. https://doi.org/10.1089/jir.2022.0185 (2023).", "volume": "43", "year": "2023" }, { "DOI": "10.3390/ijms24076142", "doi-asserted-by": "publisher", "key": "31048_CR35", "unstructured": "Mohd Zawawi, Z. et al. Prospective Roles of Tumor Necrosis Factor-Alpha (TNF-α) in COVID-19: Prognosis, Therapeutic and Management. Int. J. Mol. Sci. 24, https://doi.org/10.3390/ijms24076142 (2023)." }, { "DOI": "10.1007/s40265-022-01803-2", "author": "A Plocque", "doi-asserted-by": "publisher", "first-page": "1", "journal-title": "Drugs", "key": "31048_CR36", "unstructured": "Plocque, A. et al. Should we interfere with the Interleukin-6 receptor during COVID-19: what do we know so far? Drugs. 83, 1–36. https://doi.org/10.1007/s40265-022-01803-2 (2023).", "volume": "83", "year": "2023" }, { "DOI": "10.1007/s10875-020-00899-z", "author": "W Udomsinprasert", "doi-asserted-by": "publisher", "first-page": "11", "journal-title": "J. Clin. Immunol.", "key": "31048_CR37", "unstructured": "Udomsinprasert, W., Jittikoon, J., Sangroongruangsri, S. & Chaikledkaew, U. Circulating levels of Interleukin-6 and Interleukin-10, but not tumor necrosis Factor-Alpha, as potential biomarkers of severity and mortality for COVID-19: systematic review with Meta-analysis. J. Clin. Immunol. 41, 11–22. https://doi.org/10.1007/s10875-020-00899-z (2021).", "volume": "41", "year": "2021" }, { "DOI": "10.7150/ijbs.51811", "author": "PT Goud", "doi-asserted-by": "publisher", "first-page": "62", "journal-title": "Int. J. Biol. Sci.", "key": "31048_CR38", "unstructured": "Goud, P. T., Bai, D. & Abu-Soud, H. M. A Multiple-Hit hypothesis involving reactive oxygen species and myeloperoxidase explains clinical deterioration and fatality in COVID-19. Int. J. Biol. Sci. 17, 62–72. https://doi.org/10.7150/ijbs.51811 (2021).", "volume": "17", "year": "2021" }, { "DOI": "10.7754/Clin.Lab.2022.220416", "doi-asserted-by": "publisher", "key": "31048_CR39", "unstructured": "Esmaeili-Nadimi, A. et al. Total Antioxidant Capacity and Total Oxidant Status and Disease Severity in a Cohort Study of COVID-19 Patients. Clin. Lab. 69, https://doi.org/10.7754/Clin.Lab.2022.220416 (2023)." }, { "DOI": "10.1016/j.nmni.2021.100897", "author": "B Karkhanei", "doi-asserted-by": "publisher", "first-page": "100897", "journal-title": "New. Microbes new. Infections", "key": "31048_CR40", "unstructured": "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 Infections. 42, 100897. https://doi.org/10.1016/j.nmni.2021.100897 (2021).", "volume": "42", "year": "2021" }, { "DOI": "10.59556/japi.72.0575", "author": "M Jindal", "doi-asserted-by": "publisher", "first-page": "36", "journal-title": "J. Assoc. Phys. India", "key": "31048_CR41", "unstructured": "Jindal, M., Lehl, S. S., Jaswal, S., Bhardwaj, N. & Gupta, M. Total antioxidant status and oxidative stress in patients with COVID-19 infection. J. Assoc. Phys. India. 72, 36–39. https://doi.org/10.59556/japi.72.0575 (2024).", "volume": "72", "year": "2024" }, { "DOI": "10.4103/2045-9912.385414", "author": "H Zhang", "doi-asserted-by": "publisher", "first-page": "39", "journal-title": "Med. Gas Res.", "key": "31048_CR42", "unstructured": "Zhang, H., Zhang, C., Hua, W. & Chen, J. Saying no to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia. Med. Gas Res. 14, 39–47. https://doi.org/10.4103/2045-9912.385414 (2024).", "volume": "14", "year": "2024" }, { "DOI": "10.3389/fmicb.2023.1277552", "author": "Y Zhao", "doi-asserted-by": "publisher", "first-page": "1277552", "journal-title": "Front. Microbiol.", "key": "31048_CR43", "unstructured": "Zhao, Y. et al. Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases? Front. Microbiol. 14, 1277552. https://doi.org/10.3389/fmicb.2023.1277552 (2023).", "volume": "14", "year": "2023" }, { "DOI": "10.1016/j.amjms.2022.04.015", "author": "VP Jani", "doi-asserted-by": "publisher", "first-page": "251", "journal-title": "Am. J. Med. Sci.", "key": "31048_CR44", "unstructured": "Jani, V. P., Munoz, C. J., Govender, K., Williams, A. T. & Cabrales, P. Implications of microvascular dysfunction and nitric oxide mediated inflammation in severe COVID-19 infection. Am. J. Med. Sci. 364, 251–256. https://doi.org/10.1016/j.amjms.2022.04.015 (2022).", "volume": "364", "year": "2022" }, { "DOI": "10.7759/cureus.23852", "author": "A Ghosh", "doi-asserted-by": "publisher", "first-page": "e23852", "journal-title": "Cureus", "key": "31048_CR45", "unstructured": "Ghosh, A., Joseph, B. & Anil, S. Nitric oxide in the management of respiratory consequences in COVID-19: A scoping review of a different treatment approach. Cureus 14, e23852. https://doi.org/10.7759/cureus.23852 (2022).", "volume": "14", "year": "2022" }, { "DOI": "10.1088/1752-7163/abc302", "author": "FLM Ricciardolo", "doi-asserted-by": "publisher", "first-page": "014001", "journal-title": "J. Breath Res.", "key": "31048_CR46", "unstructured": "Ricciardolo, F. L. M., Bertolini, F., Carriero, V. & Högman, M. Nitric oxide’s physiologic effects and potential as a therapeutic agent against COVID-19. J. Breath Res. 15, 014001. https://doi.org/10.1088/1752-7163/abc302 (2020).", "volume": "15", "year": "2020" }, { "DOI": "10.1002/jbt.23536", "author": "E Erbaş", "doi-asserted-by": "publisher", "first-page": "e23536", "journal-title": "J. Biochem. Mol. Toxicol.", "key": "31048_CR47", "unstructured": "Erbaş, E., Celep, N. A., Tekiner, D., Genç, A. & Gedikli, S. Assessment of toxicological effects of favipiravir (T-705) on the lung tissue of rats: an experimental study. J. Biochem. Mol. Toxicol. 38, e23536. https://doi.org/10.1002/jbt.23536 (2024).", "volume": "38", "year": "2024" }, { "DOI": "10.1038/s41586-023-06649-6", "author": "T Sanderson", "doi-asserted-by": "publisher", "first-page": "594", "journal-title": "Nature", "key": "31048_CR48", "unstructured": "Sanderson, T. et al. A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes. Nature 623, 594–600. https://doi.org/10.1038/s41586-023-06649-6 (2023).", "volume": "623", "year": "2023" } ], "reference-count": 48, "references-count": 48, "relation": {}, "resource": { "primary": { "URL": "https://www.nature.com/articles/s41598-025-31048-4" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Evaluation of the cardiopulmonary effects of repurposed COVID-19 therapeutics in healthy rats", "type": "journal-article", "update-policy": "https://doi.org/10.1007/springer_crossmark_policy", "volume": "16" }