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Open AccessFeature PaperArticle

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

1
Department of Obstetrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands
2
Department of Developmental Origins of Disease (DDOD), Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands
3
Department of Nephrology and Hypertension, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands
4
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA
5
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
6
NIHR Southampton Biomedical Research Center, Southampton General Hospital, Southampton SO16 6YD, UK
7
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(2), 302; https://doi.org/10.3390/biom10020302
Received: 29 January 2020 / Accepted: 12 February 2020 / Published: 14 February 2020
(This article belongs to the Special Issue Hydrogen Sulfide-Based Therapeutics)
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 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24h), 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.
Keywords: blood pressure; cardiovascular; Dahl salt-sensitive rats; fetal growth restriction; hydrogen sulfide; preeclampsia; sodium thiosulfate; therapeutics blood pressure; cardiovascular; Dahl salt-sensitive rats; fetal growth restriction; hydrogen sulfide; preeclampsia; sodium thiosulfate; therapeutics
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Terstappen, F.; Clarke, S.M.; Joles, J.A.; Ross, C.A.; Garrett, M.R.; Minnion, M.; Feelisch, M.; Goor, H.; Sasser, J.M.; Lely, A.T. Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia. Biomolecules 2020, 10, 302.

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