{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:24:20Z","timestamp":1785291860212,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"\n Abstract<\/jats:title>\n \n Sodium thiosulfate (STS) is gaining increasing attention in research for its potential therapeutic applications across a spectrum of disease processes beyond its current uses. However, the precise mechanisms of action remain incompletely understood. We investigated the efficacy of STS in treating hyperglycaemia\u2010induced pronephros damage in zebrafish to gain further insight into the underlying mechanisms. Hyperglycaemia was induced in zebrafish by suppressing the\n pdx1<\/jats:italic>\n transcription factor, which plays a crucial role in maintaining physiological pancreatic function. STS was administered by introducing it into the medium of zebrafish larvae. The pronephros structure was analysed at 48\u00a0h post\u2010fertilization. Metabolomic profiling and RNA sequencing were conducted on groups exposed to various experimental conditions. Our findings reveal a downregulation of nitric oxide (NO) signalling in zebrafish with a knocked\u2010down\n pdx1<\/jats:italic>\n gene, both metabolomically and transcriptionally. Notably, treatment with STS led to a compensatory upregulation of the NO signalling, ultimately resulting in the rescue of the pronephros structure. Our study provides compelling evidence that targeting NO metabolism by the administration of STS offers a promising strategy for addressing hyperglycaemia\u2010induced organ damage. These findings underscore the potential of STS as a promising therapeutic agent for diabetic complications and warrant further investigation of its clinical applications.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Sodium thiosulfate (STS) is increasingly drawing attention in research for its potential therapeutic applications across a spectrum of disease processes.<\/jats:p>\n <\/jats:list-item>\n \n Here, we demonstrate that STS treatment rescues hyperglycaemia\u2010induced pronephros damage in zebrafish.<\/jats:p>\n <\/jats:list-item>\n \n We identified upregulation of nitric oxide signalling as the major driver behind STS\u2010mediated rescue.<\/jats:p>\n <\/jats:list-item>\n \n Our data suggest that STS offers a promising strategy for addressing hyperglycaemia\u2010induced organ damage, including diabetic nephropathy.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp286398","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T11:02:12Z","timestamp":1726138932000},"page":"4247-4260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sodium thiosulfate treatment rescues hyperglycaemia\u2010induced pronephros damage in zebrafish by upregulating nitric oxide signalling"],"prefix":"10.1113","volume":"604","author":[{"given":"Hannes","family":"Ott","sequence":"first","affiliation":[{"name":"Department of Vascular Biology and Tumor Angiogenesis European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Bennewitz","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Tumor Angiogenesis European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Tumor Angiogenesis European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariia","family":"Prianichnikova","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Tumor Angiogenesis European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Sticht","sequence":"additional","affiliation":[{"name":"NGS Core Facility, Medical Faculty Mannheim Heidelberg University Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Poschet","sequence":"additional","affiliation":[{"name":"Metabolomics Core Technology Platform Centre for Organismal Studies Heidelberg University Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0908-2156","authenticated-orcid":false,"given":"Jens","family":"Kroll","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Tumor Angiogenesis European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms130911288"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.2.43"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-1241-0"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124881"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801109"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.209783"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158452"},{"key":"e_1_2_5_10_1","unstructured":"Carlson M.(2019).org.Dr.eg.db: Genome Wide Annotation for Zebrafish. 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