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Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia

Aberrant production of hydrogen sulfide (H(2)S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H(2)S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preecla...

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Autores principales: Terstappen, Fieke, Clarke, Sinéad M., Joles, Jaap A., Ross, Courtney A, Garrett, Michael R., Minnion, Magdalena, Feelisch, Martin, van Goor, Harry, Sasser, Jennifer M., Lely, A. Titia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072460/
https://www.ncbi.nlm.nih.gov/pubmed/32075042
http://dx.doi.org/10.3390/biom10020302
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author Terstappen, Fieke
Clarke, Sinéad M.
Joles, Jaap A.
Ross, Courtney A
Garrett, Michael R.
Minnion, Magdalena
Feelisch, Martin
van Goor, Harry
Sasser, Jennifer M.
Lely, A. Titia
author_facet Terstappen, Fieke
Clarke, Sinéad M.
Joles, Jaap A.
Ross, Courtney A
Garrett, Michael R.
Minnion, Magdalena
Feelisch, Martin
van Goor, Harry
Sasser, Jennifer M.
Lely, A. Titia
author_sort Terstappen, Fieke
collection PubMed
description Aberrant production of hydrogen sulfide (H(2)S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H(2)S 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 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24 h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 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.
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spelling pubmed-70724602020-03-19 Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia Terstappen, Fieke Clarke, Sinéad M. Joles, Jaap A. Ross, Courtney A Garrett, Michael R. Minnion, Magdalena Feelisch, Martin van Goor, Harry Sasser, Jennifer M. Lely, A. Titia Biomolecules Article Aberrant production of hydrogen sulfide (H(2)S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H(2)S 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 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24 h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 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. MDPI 2020-02-14 /pmc/articles/PMC7072460/ /pubmed/32075042 http://dx.doi.org/10.3390/biom10020302 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Terstappen, Fieke
Clarke, Sinéad M.
Joles, Jaap A.
Ross, Courtney A
Garrett, Michael R.
Minnion, Magdalena
Feelisch, Martin
van Goor, Harry
Sasser, Jennifer M.
Lely, A. Titia
Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia
title Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia
title_full Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia
title_fullStr Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia
title_full_unstemmed Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia
title_short Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia
title_sort sodium thiosulfate in the pregnant dahl salt-sensitive rat, a model of preeclampsia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072460/
https://www.ncbi.nlm.nih.gov/pubmed/32075042
http://dx.doi.org/10.3390/biom10020302
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