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Discovery of physiological roles of H<jats:sub>2<\/jats:sub>S as a neurotransmitter by Kimura and colleagues triggered an intensive research in the biological roles of H<jats:sub>2<\/jats:sub>S in the past decades. Manipulation of H<jats:sub>2<\/jats:sub>S levels by inhibiting H<jats:sub>2<\/jats:sub>S synthesis or administration of H<jats:sub>2<\/jats:sub>S-releasing molecules revealed beneficial as well as harmful effects of H<jats:sub>2<\/jats:sub>S. As a result, it is now established that H<jats:sub>2<\/jats:sub>S levels are tightly controlled and too much or too little H<jats:sub>2<\/jats:sub>S levels cause harm. Nonetheless, translation of sulfide-based therapy to clinical practice has been stymied due to the very low therapeutic index of sulfide and the incomplete understanding of endogenous sulfide metabolism. One potential strategy to circumvent this problem is to use a safe and stable sulfide metabolite that may mediate effects of H<jats:sub>2<\/jats:sub>S. Alternatively, endogenous sulfide levels may be controlled using specific sulfide scavengers. In this review article, the role of endogenous H<jats:sub>2<\/jats:sub>S production and catabolism will be briefly reviewed followed by an introduction of thiosulfate and H<jats:sub>2<\/jats:sub>S scavengers as novel pharmacological tools to control H<jats:sub>2<\/jats:sub>S-dependent signaling.<\/jats:p>","DOI":"10.1186\/s40635-020-0296-4","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T19:02:59Z","timestamp":1580497379000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness"],"prefix":"10.1186","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7031-7386","authenticated-orcid":false,"given":"Eizo","family":"Marutani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumito","family":"Ichinose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"key":"296_CR1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1146\/annurev.pa.32.040192.000545","volume":"32","author":"RJ Reiffenstein","year":"1992","unstructured":"Reiffenstein RJ, Hulbert WC, Roth SH (1992) Toxicology of hydrogen sulfide. 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