{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:58:30Z","timestamp":1785869910274,"version":"3.56.0"},"reference-count":199,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medicine of Madrid Complutense University","award":["UCM-911757"],"award-info":[{"award-number":["UCM-911757"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review integrates the biology and clinical translation of hydrogen sulfide (H2S) in balneology. It frames H2S as a gasotransmitters with dual chemical and biological actions and summarizes the H2S\/HS\u2212 equilibrium as a function of pH, temperature, and oxygenation, which governs bioaccessibility in sulfurous waters. Endogenous and exogenous sources, transport, and mitochondrial catabolism are outlined, together with core cellular mechanisms: protein persulfidation; activation of Nrf2\/ARE; modulation of NF-\u03baB; regulation of ion channels; and engagement of PI3K\/Akt, MAPK\/ERK, and Wnt pathways, plus epigenetic interactions with HDACs and sirtuins. Preclinical and clinical evidence in dermatology, musculoskeletal disease, and respiratory care is synthesized, alongside metabolic, cardiovascular, gastrointestinal, and renal effects. Technical aspects that preserve the bioactive fraction of H2S while meeting environmental safety limits are highlighted. Routes of administration (bathing, peloids, inhalation, and drinking cures) and key operational parameters are described. Overall, the review links physicochemical and molecular foundations with clinical indications for sulfurous waters and derivatives and identifies opportunities for research and development in H2S donors and thermal cosmetics without extrapolating beyond the available data.<\/jats:p>","DOI":"10.3390\/ijms262110790","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:08:51Z","timestamp":1762423731000},"page":"10790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hydrogen Sulfide in Balneology: Physiology, Evidence, and Clinical Translation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-9647","authenticated-orcid":false,"given":"Jose Manuel","family":"Carbajo","sequence":"first","affiliation":[{"name":"Medical Hydrology Group, Department of Radiology and Rehabilitation, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3818-6624","authenticated-orcid":false,"given":"Francisco","family":"Maraver","sequence":"additional","affiliation":[{"name":"Medical Hydrology Group, Department of Radiology and Rehabilitation, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"},{"name":"Professional School of Medical Hydrology, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7254-4152","authenticated-orcid":false,"given":"Lorena","family":"Vela","sequence":"additional","affiliation":[{"name":"Medical Hydrology Group, Department of Radiology and Rehabilitation, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"},{"name":"Professional School of Medical Hydrology, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1084-7710","authenticated-orcid":false,"given":"Constantin","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Faculty of Medical Bioengineering, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d Ia\u0219i, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1152\/physrev.00017.2011","article-title":"Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed","volume":"92","author":"Wang","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1089\/ars.2014.5869","article-title":"Signaling Molecules: Hydrogen Sulfide and Polysulfide","volume":"22","author":"Kimura","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nrd2425","article-title":"Hydrogen Sulphide and Its Therapeutic Potential","volume":"6","year":"2007","journal-title":"Nat. Rev. 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