{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:03:20Z","timestamp":1790532200118,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University Plovdiv","award":["15-2025"],"award-info":[{"award-number":["15-2025"]}]},{"name":"Medical University Plovdiv","award":["BG-RRP-2.004-0007-C01"],"award-info":[{"award-number":["BG-RRP-2.004-0007-C01"]}]},{"name":"Medical University Plovdiv","award":["D01-165\/28.07.2022"],"award-info":[{"award-number":["D01-165\/28.07.2022"]}]},{"name":"Medical University Plovdiv","award":["D01-371\/15.12.2023"],"award-info":[{"award-number":["D01-371\/15.12.2023"]}]},{"name":"NextGeneration EU","award":["15-2025"],"award-info":[{"award-number":["15-2025"]}]},{"name":"NextGeneration EU","award":["BG-RRP-2.004-0007-C01"],"award-info":[{"award-number":["BG-RRP-2.004-0007-C01"]}]},{"name":"NextGeneration EU","award":["D01-165\/28.07.2022"],"award-info":[{"award-number":["D01-165\/28.07.2022"]}]},{"name":"NextGeneration EU","award":["D01-371\/15.12.2023"],"award-info":[{"award-number":["D01-371\/15.12.2023"]}]},{"name":"BBMRI","award":["15-2025"],"award-info":[{"award-number":["15-2025"]}]},{"name":"BBMRI","award":["BG-RRP-2.004-0007-C01"],"award-info":[{"award-number":["BG-RRP-2.004-0007-C01"]}]},{"name":"BBMRI","award":["D01-165\/28.07.2022"],"award-info":[{"award-number":["D01-165\/28.07.2022"]}]},{"name":"BBMRI","award":["D01-371\/15.12.2023"],"award-info":[{"award-number":["D01-371\/15.12.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is an autoimmune disease affecting the synovium. Mitochondrial dysfunction is considered a critical factor in the pathogenesis of RA. The aim of the study was to determine the effect of methotrexate and tofacitinib on mitochondrial function and oxidative stress in an in vitro study on the model synovial cell line SW982. TNF-alpha-stimulated SW982 cells, as well as control untreated cells, were incubated with methotrexate and tofacitinib. A metabolic test was performed to assess mitochondrial function. The oxidative stress generated after the application of the therapeutics was determined by a chromatographic analysis. The results obtained showed an increase in ATP levels (p &lt; 0.0001) and a decrease in proton leak (p &lt; 0.0003) after treatment with tofacitinib. The opposite trend was observed\u2014reduced ATP production (p &lt; 0.0096) and increased levels of proton leak (p &lt; 0.0001)\u2014after treatment with methotrexate. A two-fold increase in 8-ISOPGF2A was measured in comparison to TNF-alpha-stimulated and untreated cells. The dynamics of mitochondrial activity and oxidative stress were monitored in a certified RA model cell line after the administration of two different therapeutics. Methotrexate was found to induce mitochondrial dysfunction and oxidative stress in vitro, while tofacitinib partially improved mitochondrial parameters.<\/jats:p>","DOI":"10.3390\/ijms26178173","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T15:57:47Z","timestamp":1755878267000},"page":"8173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Methotrexate and Tofacitinib on Mitochondrial Function and Oxidative Stress in Human Synovial Cells In Vitro"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3845-2072","authenticated-orcid":false,"given":"Valentina","family":"Mihaylova","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Medical University, Blvd. Vasil Aprilov 15A, 4000 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-9855","authenticated-orcid":false,"given":"Desislav","family":"Tomov","sequence":"additional","affiliation":[{"name":"Research Institute, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rositsa","family":"Karalilova","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Clinic of Rheumatology, University Hospital \u201cKaspela\u201d, 4001 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zguro","family":"Batalov","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Clinic of Rheumatology, University Hospital \u201cKaspela\u201d, 4001 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastas","family":"Batalov","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Clinic of Rheumatology, University Hospital \u201cKaspela\u201d, 4001 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1501-0175","authenticated-orcid":false,"given":"Victoria","family":"Sarafian","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical University, Blvd. Vasil Aprilov 15A, 4000 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical University, Blvd. Vasil Aprilov 15A, 4000 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Radu, A.F., and Bungau, S.G. 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