{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:37:53Z","timestamp":1790091473480,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe\u2212\/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.<\/jats:p>","DOI":"10.3390\/ijms22063258","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T14:08:16Z","timestamp":1616508496000},"page":"3258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Pharmacology and Therapeutic Utility of Sodium Hydroselenide"],"prefix":"10.3390","volume":"22","author":[{"given":"Kavitej","family":"Samra","sequence":"first","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathun","family":"Kuganesan","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Smith","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kleyman","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Tidswell","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishkantha","family":"Arulkumaran","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervyn","family":"Singer","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-9432","authenticated-orcid":false,"given":"Alex","family":"Dyson","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1096\/fj.02-0211hyp","article-title":"Two\u2019s Company, Three\u2019s a Crowd: Can H2S Be the Third Endogenous Gaseous Transmitter?","volume":"16","author":"Wang","year":"2002","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1126\/science.1108581","article-title":"H2S Induces a Suspended Animation-like State in Mice","volume":"308","author":"Blackstone","year":"2005","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrd4433","article-title":"Hydrogen Sulfide-based Therapeutics: Exploiting a Unique but Ubiquitous Gasotransmitter","volume":"14","author":"Wallace","year":"2015","journal-title":"Nat. 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