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; Goor, Harry van; Sasser, Jennifer M; Lely, A Titia
(2020) Biomolecules, volume 10, issue 2
(Article)
Abstract
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),
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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.
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Keywords: Blood pressure, Cardiovascular, Dahl salt-sensitive rats, Fetal growth restriction, Hydrogen sulfide, Preeclampsia, Sodium thiosulfate, Therapeutics, blood pressure, therapeutics, preeclampsia, cardiovascular, sodium thiosulfate, fetal growth restriction, hydrogen sulfide, Molecular Biology, Biochemistry
ISSN: 2218-273X
Publisher: Multidisciplinary Digital Publishing Institute
Note: Funding Information: Funding: This study was supported by the Dutch Kidney Foundation, grant number 15O141 (ATL) and 17OKK54 (SMC), ZonMw, grant number 40‐000703‐97‐12463 (ATL) and 114024055 (FT/ATL), and the National Institutes of Health, grant number R01HL134711 (JMS) and R01HL137673 (MRG). Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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