{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:35:17Z","timestamp":1791974117293,"version":"4.4.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T00:00:00Z","timestamp":1581638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","award":["15O141"],"award-info":[{"award-number":["15O141"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","award":["17OKK54"],"award-info":[{"award-number":["17OKK54"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["40-000703-97-12463"],"award-info":[{"award-number":["40-000703-97-12463"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["114024055"],"award-info":[{"award-number":["114024055"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL134711"],"award-info":[{"award-number":["R01HL134711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL137673"],"award-info":[{"award-number":["R01HL137673"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aberrant production of hydrogen sulfide (H2S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H2S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia. In addition to a control group (n = 13), two groups received STS via drinking water at a dose of 2 g (n = 9) or 3 g per kg body weight per day (n = 8) from gestational day (GD) 10 to 20. Uterine artery resistance index was measured (GD18), urinary protein excretion rate was determined (GD19), and blood pressure and fetal outcomes were evaluated (GD20). At 2 g, STS had no effect on preeclamptic symptoms or fetal outcome. At 3 g, STS reduced maternal hypertension (121.8 \u00b1 3.0 vs. 136.3 \u00b1 2.9), but increased proteinuria (89 \u00b1 15 vs. 56 \u00b1 5 mg\/24 h), and relative kidney weight (0.86 \u00b1 0.04 vs. 0.73 \u00b1 0.02%). Fetal\/placental weight ratio was reduced (3.83 \u00b1 0.07 vs. 4.31 \u00b1 0.08) without affecting litter size. No differences in uterine artery flow or renal histological damage were noted across treatment groups. While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the unfavorable effects on proteinuria, kidney weight, and fetal\/placental weight ratio implies that clinical implementation of STS is contra-indicated until safety for mother and child can be verified.<\/jats:p>","DOI":"10.3390\/biom10020302","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T10:49:16Z","timestamp":1582282156000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6587-1320","authenticated-orcid":false,"given":"Fieke","family":"Terstappen","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands"},{"name":"Department of Developmental Origins of Disease (DDOD), Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin\u00e9ad M.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2565-242X","authenticated-orcid":false,"given":"Jaap A.","family":"Joles","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney A","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Minnion","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"NIHR Southampton Biomedical Research Center, Southampton General Hospital, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Feelisch","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"NIHR Southampton Biomedical Research Center, Southampton General Hospital, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-1577","authenticated-orcid":false,"given":"Harry","family":"van Goor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7161-5502","authenticated-orcid":false,"given":"Jennifer M.","family":"Sasser","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Titia","family":"Lely","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S0140-6736(06)68397-9","article-title":"Van WHO analysis of causes of maternal death: A systematic review","volume":"367","author":"Khan","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nrneph.2014.102","article-title":"Pre-eclampsia part 1: Current understanding of its pathophysiology","volume":"10","author":"Chaiworapongsa","year":"2014","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1161\/HYPERTENSIONAHA.117.10803","article-title":"Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice","volume":"72","author":"Brown","year":"2018","journal-title":"Hypertension"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1053\/j.ajkd.2009.12.036","article-title":"Kidney Disease After Preeclampsia: A Systematic Review","volume":"55","author":"Mcdonald","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(05)17987-2","article-title":"Pre-eclampsia","volume":"365","author":"Sibai","year":"2005","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1161\/HYPERTENSIONAHA.116.06603","article-title":"The Developmental Programming of Hypertension: Physiological Mechanisms","volume":"68","author":"Dasinger","year":"2016","journal-title":"Hypertension"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1111\/1471-0528.15180","article-title":"Angiogenic factors in pre-eclampsia: Implications for clinical practice","volume":"125","author":"Karumanchi","year":"2018","journal-title":"BJOG"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1161\/CIRCULATIONAHA.113.001631","article-title":"Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine gamma-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia","volume":"127","author":"Wang","year":"2013","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/MNH.0000000000000096","article-title":"Hydrogen sulfide: Role in vascular physiology and pathology","volume":"24","author":"Holwerda","year":"2015","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.ajpath.2013.01.001","article-title":"Reduced cystathionine gamma-lyase and increased miR-21 expression are associated with increased vascular resistance in growth-restricted pregnancies: Hydrogen sulfide as a placental vasodilator","volume":"182","author":"Herrera","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.placenta.2012.02.014","article-title":"Hydrogen sulfide producing enzymes in pregnancy and preeclampsia","volume":"33","author":"Holwerda","year":"2012","journal-title":"Placenta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.placenta.2017.02.012","article-title":"MiR133b is involved in endogenous hydrogen sulfide suppression of sFlt-1 production in human placenta","volume":"52","author":"Hu","year":"2017","journal-title":"Placenta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/biolre\/iox105","article-title":"Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis","volume":"97","author":"Chen","year":"2017","journal-title":"Biol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.bcp.2012.10.019","article-title":"Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras","volume":"85","author":"Kashfi","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s00210-016-1296-5","article-title":"Sodium hydrosulfide prevents hypertension and increases in vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 in hypertensive pregnant rats","volume":"389","author":"Graca","year":"2016","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1111\/bph.12825","article-title":"Exogenous administration of thiosulfate, a donor of hydrogen sulfide, attenuates angiotensin II-induced hypertensive heart disease","volume":"172","author":"Snijder","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1042\/bj1030791","article-title":"Thiosulphate Oxidation by Rat Liver Mitochondria in the Presence of Glutathione","volume":"103","author":"Koj","year":"1967","journal-title":"Biochem. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.33549\/physiolres.932363","article-title":"Age-Dependent Salt Hypertension in Dahl Rats: Fifty Years of Research","volume":"61","author":"Zicha","year":"2012","journal-title":"Physiol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rapp, J.P., and Garrett, M.R. (2019). Will the Real Dahl S Rat Please Stand Up?. Am. J. Physiol. Physiol.","DOI":"10.1152\/ajprenal.00359.2019"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1152\/ajpregu.00377.2014","article-title":"The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia","volume":"309","author":"Gillis","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1152\/ajpregu.90875.2008","article-title":"Asymmetric dimethylarginine in angiotensin II-induced hypertension","volume":"298","author":"Sasser","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_22","first-page":"754","article-title":"Determinants of focal and segmental glomerulosclerosis in the rat after renal ablation. Evidence for involvement of macrophages and lipids","volume":"64","author":"Fidler","year":"1991","journal-title":"Lab Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1177\/0192623318755135","article-title":"Histomorphologic Analysis of the Late-term Rat Fetus and Placenta","volume":"46","author":"Charest","year":"2018","journal-title":"Toxicol. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1152\/ajpregu.00198.2009","article-title":"Effects of sildenafil on maternal hemodynamics and fetal growth in normal rat pregnancy","volume":"298","author":"Sasser","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1097\/00004872-200310000-00015","article-title":"The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase","volume":"21","author":"Zhong","year":"2013","journal-title":"J. Hypertens."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/ajh.2011.149","article-title":"Interdependency of Cystathione \u03b3-Lyase and Cystathione \u03b2-Synthase in Hydrogen Sulfide\u2013Induced Blood Pressure Regulation in Rats","volume":"25","author":"Roy","year":"2012","journal-title":"Am. J. Hypertens."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ejogrb.2005.09.007","article-title":"Oral N -acetylcysteine administration does not stabilise the process of established severe preeclampsia","volume":"127","author":"Roes","year":"2006","journal-title":"Eur. J. Obs. Gynecol. Reprod. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1089\/ars.2013.5354","article-title":"Cystathionine \u03b3-lyase deficiency protects mice from galactosamine\/lipopolysaccharide-induced acute liver failure","volume":"20","author":"Shirozu","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1089\/ars.2011.4363","article-title":"Inhaled Hydrogen Sulfide Prevents Endotoxin-Induced Systemic Inflammation and Improves Survival by Altering Sulfide Metabolism in Mice","volume":"17","author":"Tokuda","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1161\/HYPERTENSIONAHA.115.06071","article-title":"Sildenafil Treatment Ameliorates the Maternal Syndrome of Preeclampsia and Rescues Fetal Growth in the Dahl Salt-Sensitive Rat","volume":"67","author":"Gillis","year":"2016","journal-title":"Hypertension"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/GRF.0000000000000254","article-title":"Controversies Regarding Diagnosis and Treatment of Severe Hypertension in Pregnancy","volume":"60","author":"Barton","year":"2017","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s00404-012-2371-x","article-title":"Nifedipine versus labetalol in the treatment of hypertensive disorders of pregnancy","volume":"286","author":"Giannubilo","year":"2012","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/184994a0","article-title":"Thiosulphate Metabolism in the Animal Organism","volume":"184","author":"Donhoffer","year":"1959","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1152\/ajpregu.00421.2012","article-title":"Thiosulfate: A readily accessible source of hydrogen sulfide in oxygen sensing","volume":"305","author":"Olson","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/2\/302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:57:48Z","timestamp":1760173068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/2\/302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,14]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["biom10020302"],"URL":"https:\/\/doi.org\/10.3390\/biom10020302","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,14]]}}}