{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:55:37Z","timestamp":1787849737076,"version":"build-2784847793"},"reference-count":88,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016168","name":"Ludwig Boltzmann Gesellschaft","doi-asserted-by":"publisher","award":["x"],"award-info":[{"award-number":["x"]}],"id":[{"id":"10.13039\/501100016168","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hydrogen sulfide (H2S) is an important mediator of inflammatory processes. However, controversial findings also exist, and its underlying molecular mechanisms are largely unknown. Recently, the byproducts of H2S, per-\/polysulfides, emerged as biological mediators themselves, highlighting the complex chemistry of H2S. In this study, we characterized the biological effects of P*, a slow-releasing H2S and persulfide donor. To differentiate between H2S and polysulfide-derived effects, we decomposed P* into polysulfides. P* was further compared to the commonly used fast-releasing H2S donor sodium hydrogen sulfide (NaHS). The effects on oxidative stress and interleukin-6 (IL-6) expression were assessed in ATDC5 cells using superoxide measurement, qPCR, ELISA, and Western blotting. The findings on IL-6 expression were corroborated in primary chondrocytes from osteoarthritis patients. In ATDC5 cells, P* not only induced the expression of the antioxidant enzyme heme oxygenase-1 via per-\/polysulfides, but also induced activation of Akt and p38 MAPK. NaHS and P* significantly impaired menadione-induced superoxide production. P* reduced IL-6 levels in both ATDC5 cells and primary chondrocytes dependent on H2S release. Taken together, P* provides a valuable research tool for the investigation of H2S and per-\/polysulfide signaling. These data demonstrate the importance of not only H2S, but also per-\/polysulfides as bioactive signaling molecules with potent anti-inflammatory and, in particular, antioxidant properties.<\/jats:p>","DOI":"10.3390\/antiox10071049","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"1049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of the Inducible and Slow-Releasing Hydrogen Sulfide and Persulfide Donor P*: Insights into Hydrogen Sulfide Signaling"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-9639","authenticated-orcid":false,"given":"Modesta","family":"Trummer","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria"},{"name":"Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, Karl-Franzens-University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4371-6119","authenticated-orcid":false,"given":"Erwan","family":"Galardon","sequence":"additional","affiliation":[{"name":"UMR 8601, LCBPT, CNRS-Universit\u00e9 de Paris, 75270 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Fischer","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria"},{"name":"Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Toegel","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria"},{"name":"Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, Karl-Franzens-University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guenter","family":"Steiner","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria"},{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Kloesch","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria"},{"name":"Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, Karl-Franzens-University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0140-6736(14)60802-3","article-title":"Osteoarthritis","volume":"386","author":"Palmer","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthr. 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