{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:30:28Z","timestamp":1789050628273,"version":"build-2803163510"},"reference-count":72,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovak Grant Agencies VEGA and APVV","award":["VEGA No. 2\/0079\/24"],"award-info":[{"award-number":["VEGA No. 2\/0079\/24"]}]},{"name":"Slovak Grant Agencies VEGA and APVV","award":["VEGA No. 2\/0091\/23"],"award-info":[{"award-number":["VEGA No. 2\/0091\/23"]}]},{"name":"Slovak Grant Agencies VEGA and APVV","award":["VEGA No. 2\/0126\/23"],"award-info":[{"award-number":["VEGA No. 2\/0126\/23"]}]},{"name":"Slovak Grant Agencies VEGA and APVV","award":["APVV-15-0308"],"award-info":[{"award-number":["APVV-15-0308"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and systemic involvement. This study investigates the therapeutic potential of oral hyaluronan (HA) with different molecular weights (SHA: 0.99 MDa and VHA: 1.73 MDa) as monotherapy and in combination with methotrexate (MTX) in a preclinical adjuvant arthritis (AA) model in Lewis rats. The aim was to evaluate the impact of these treatments on biometric, inflammatory, and oxidative stress parameters. The preliminary study tested two doses of HA (0.5 mg\/kg and 5 mg\/kg), and the pivotal study focused on the combination of 0.5 mg\/kg HA with 0.3 mg\/kg MTX. Based on our experimental findings on combined therapy, the MTX + SHA combination demonstrated superior efficacy compared to MTX + VHA and MTX monotherapy. Specifically, the MTX + SHA regimen significantly promoted weight gain and reduced hind-paw volume in all monitored experimental days. This treatment markedly reduced plasmatic IL-17A levels (day 21) and GGT activity in both the spleen and joints (day 28), showing the most pronounced effects among all groups, including the MTX monotherapy group. The MTX + VHA combination showed a therapeutic response comparable to MTX alone, indicating no additional benefit. These findings suggest a superior efficacy of the MTX + SHA combination in comparison to other studied treatments. The overall efficacy can be ranked as: MTX \u2248 MTX + VHA &lt; MTX + SHA.<\/jats:p>","DOI":"10.3390\/ijms26093958","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"3958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic Effects of Two Different Molecular Weights of Orally Administered Hyaluronan, Both as Monotherapy and in Combination with Methotrexate in a Rat Model of Arthritis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2821-2947","authenticated-orcid":false,"given":"Sasan","family":"Khademnematolahi","sequence":"first","affiliation":[{"name":"Centre of Experimental Medicine SAS, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovakia"},{"name":"Faculty of Natural Sciences, Comenius University, 814 99 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-5441","authenticated-orcid":false,"given":"Silvester","family":"Ponist","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine SAS, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Svik","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine SAS, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-5514","authenticated-orcid":false,"given":"Frantisek","family":"Drafi","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine SAS, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Slovak","sequence":"additional","affiliation":[{"name":"State Institute for Drug Control, 825 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7419-6913","authenticated-orcid":false,"given":"Jana","family":"Muchova","sequence":"additional","affiliation":[{"name":"Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5363-8716","authenticated-orcid":false,"given":"Elisabeth Louise","family":"Mindang","sequence":"additional","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, Yaound\u00e9 P.O. Box 337, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waqar","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine SAS, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovakia"},{"name":"Faculty of Natural Sciences, Comenius University, 814 99 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7863-2142","authenticated-orcid":false,"given":"Katarina","family":"Bauerova","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine SAS, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1093\/rheumatology\/ket414","article-title":"Rheumatoid arthritis pathophysiology: Update on emerging cytokine and cytokine-associated cell targets","volume":"53","author":"Furst","year":"2014","journal-title":"Rheumatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2174\/2772434418666230406083149","article-title":"Current Prospects in Rheumatoid Arthritis: Pathophysiology, Genetics, and Treatments","volume":"19","author":"Khan","year":"2024","journal-title":"Recent Adv. 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