PMID- 32075042
OWN - NLM
STAT- MEDLINE
DCOM- 20210316
LR  - 20210316
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 10
IP  - 2
DP  - 2020 Feb 14
TI  - Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of 
      Preeclampsia.
LID - 10.3390/biom10020302 [doi]
LID - 302
AB  - 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/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.
FAU - Terstappen, Fieke
AU  - Terstappen F
AD  - Department of Obstetrics, Wilhelmina Children's Hospital, University Medical 
      Center Utrecht, 3508GA Utrecht, The Netherlands.
AD  - Department of Developmental Origins of Disease (DDOD), Wilhelmina Children's 
      Hospital, University Medical Center Utrecht, 3508GA Utrecht, The Netherlands.
FAU - Clarke, Sinead M
AU  - Clarke SM
AD  - Department of Obstetrics, Wilhelmina Children's Hospital, University Medical 
      Center Utrecht, 3508GA Utrecht, The Netherlands.
FAU - Joles, Jaap A
AU  - Joles JA
AD  - Department of Nephrology and Hypertension, University Medical Center Utrecht, 
      3508GA Utrecht, The Netherlands.
FAU - Ross, Courtney A
AU  - Ross CA
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, MS 39216-4505, USA.
FAU - Garrett, Michael R
AU  - Garrett MR
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, MS 39216-4505, USA.
FAU - Minnion, Magdalena
AU  - Minnion M
AD  - Clinical and Experimental Sciences, Faculty of Medicine, University of 
      Southampton, Southampton SO16 6YD, UK.
AD  - NIHR Southampton Biomedical Research Center, Southampton General Hospital, 
      Southampton SO16 6YD, UK.
FAU - Feelisch, Martin
AU  - Feelisch M
AD  - Clinical and Experimental Sciences, Faculty of Medicine, University of 
      Southampton, Southampton SO16 6YD, UK.
AD  - NIHR Southampton Biomedical Research Center, Southampton General Hospital, 
      Southampton SO16 6YD, UK.
FAU - Goor, Harry van
AU  - Goor HV
AD  - Department of Pathology and Medical Biology, University Medical Center Groningen, 
      University of Groningen, 9713GZ Groningen, The Netherlands.
FAU - Sasser, Jennifer M
AU  - Sasser JM
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, MS 39216-4505, USA.
FAU - Lely, A Titia
AU  - Lely AT
AD  - Department of Obstetrics, Wilhelmina Children's Hospital, University Medical 
      Center Utrecht, 3508GA Utrecht, The Netherlands.
LA  - eng
GR  - 114024055/ZONMW_/ZonMw/Netherlands
GR  - 40-000703-97-12463/ZONMW_/ZonMw/Netherlands
GR  - 15O141/Nierstichting/International
GR  - 17OKK54/Nierstichting/International
GR  - R01 HL134711/HL/NHLBI NIH HHS/United States
GR  - R01 HL137673/HL/NHLBI NIH HHS/United States
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200214
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Thiosulfates)
RN  - HX1032V43M (sodium thiosulfate)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Female
MH  - Fetal Growth Retardation/metabolism
MH  - Fetus/metabolism
MH  - Hypertension/metabolism
MH  - Kidney/metabolism
MH  - Placenta/blood supply/drug effects/metabolism
MH  - Pre-Eclampsia/*drug therapy/*metabolism/physiopathology
MH  - Pregnancy
MH  - Proteinuria/metabolism
MH  - Rats
MH  - Rats, Inbred Dahl
MH  - Thiosulfates/metabolism/*pharmacology
MH  - Uterine Artery/metabolism
PMC - PMC7072460
OTO - NOTNLM
OT  - Dahl salt-sensitive rats
OT  - blood pressure
OT  - cardiovascular
OT  - fetal growth restriction
OT  - hydrogen sulfide
OT  - preeclampsia
OT  - sodium thiosulfate
OT  - therapeutics
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/02/23 06:00
MHDA- 2021/03/17 06:00
PMCR- 2020/02/01
CRDT- 2020/02/21 06:00
PHST- 2020/01/29 00:00 [received]
PHST- 2020/02/12 00:00 [accepted]
PHST- 2020/02/21 06:00 [entrez]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2021/03/17 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - biom10020302 [pii]
AID - biomolecules-10-00302 [pii]
AID - 10.3390/biom10020302 [doi]
PST - epublish
SO  - Biomolecules. 2020 Feb 14;10(2):302. doi: 10.3390/biom10020302.