PMID- 27789293
OWN - NLM
STAT- MEDLINE
DCOM- 20171229
LR  - 20180131
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 101
DP  - 2016 Dec
TI  - Molecular hydrogen ameliorates several characteristics of preeclampsia in the 
      Reduced Uterine Perfusion Pressure (RUPP) rat model.
PG  - 524-533
LID - S0891-5849(16)30978-9 [pii]
LID - 10.1016/j.freeradbiomed.2016.10.491 [doi]
AB  - Oxidative stress plays an important role in the pathogenesis of preeclampsia. 
      Recently, molecular hydrogen (H(2)) has been shown to have therapeutic potential 
      in various oxidative stress-related diseases. The aim of this study is to 
      investigate the effect of H(2) on preeclampsia. We used the reduced 
      utero-placental perfusion pressure (RUPP) rat model, which has been widely used 
      as a model of preeclampsia. H(2) water (HW) was administered orally ad libitum in 
      RUPP rats from gestational day (GD) 12-19, starting 2 days before RUPP procedure. 
      On GD19, mean arterial pressure (MAP) was measured, and samples were collected. 
      Maternal administration of HW significantly decreased MAP, and increased fetal 
      and placental weight in RUPP rats. The increased levels of soluble fms-like 
      tyrosine kinase-1 (sFlt-1) and diacron reactive oxygen metabolites as a biomarker 
      of reactive oxygen species in maternal blood were decreased by HW administration. 
      However, vascular endothelial growth factor level in maternal blood was increased 
      by HW administration. Proteinuria, and histological findings in kidney were 
      improved by HW administration. In addition, the effects of H(2) on placental 
      villi were examined by using a trophoblast cell line (BeWo) and villous explants 
      from the placental tissue of women with or without preeclampsia. H(2) 
      significantly attenuated hydrogen peroxide-induced sFlt-1 expression, but could 
      not reduce the expression induced by hypoxia in BeWo cells. H(2) significantly 
      attenuated sFlt-1 expression in villous explants from women with preeclampsia, 
      but not affected them from normotensive pregnancy. The prophylactic 
      administration of H(2) attenuated placental ischemia-induced hypertension, 
      angiogenic imbalance, and oxidative stress. These results support the theory that 
      H(2) has a potential benefit in the prevention of preeclampsia.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Ushida, Takafumi
AU  - Ushida T
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Kotani, Tomomi
AU  - Kotani T
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan. Electronic address: itoto@med.nagoya-u.ac.jp.
FAU - Tsuda, Hiroyuki
AU  - Tsuda H
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Imai, Kenji
AU  - Imai K
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Nakano, Tomoko
AU  - Nakano T
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Hirako, Shima
AU  - Hirako S
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Ito, Yumiko
AU  - Ito Y
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Li, Hua
AU  - Li H
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Mano, Yukio
AU  - Mano Y
AD  - Mano Women's Clinic, 2-5 Matsushin-cho, Kasugai city, Aichi Prefecture 486-0931, 
      Japan.
FAU - Wang, Jingwen
AU  - Wang J
AD  - Laboratory of Bell Research Center-Department of Obstetrics and Gynaecology 
      Collaborative Research, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Miki, Rika
AU  - Miki R
AD  - Laboratory of Bell Research Center-Department of Obstetrics and Gynaecology 
      Collaborative Research, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Yamamoto, Eiko
AU  - Yamamoto E
AD  - Department of Healthcare Administration, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Iwase, Akira
AU  - Iwase A
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Bando, Yasuko K
AU  - Bando YK
AD  - Department of Cardiology, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Hirayama, Masaaki
AU  - Hirayama M
AD  - Division of Neurogenetics, Center for Neurological Diseases and Cancer, 65 
      Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Ohno, Kinji
AU  - Ohno K
AD  - Division of Neurogenetics, Center for Neurological Diseases and Cancer, 65 
      Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Toyokuni, Shinya
AU  - Toyokuni S
AD  - Department of Pathology and Biological Responses, 65 Tsurumai-cho, Showa-ku, 
      Nagoya 466-8550, Japan.
FAU - Kikkawa, Fumitaka
AU  - Kikkawa F
AD  - Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161024
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 7YNJ3PO35Z (Hydrogen)
RN  - EC 2.7.10.1 (Flt1 protein, mouse)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - Animals
MH  - Blood Pressure/*drug effects
MH  - Disease Models, Animal
MH  - Female
MH  - Fetus
MH  - Gene Expression Regulation
MH  - Gestational Age
MH  - Humans
MH  - Hydrogen/*pharmacology
MH  - Organ Size/drug effects
MH  - Placenta/blood supply/drug effects/metabolism
MH  - Pre-Eclampsia/*drug therapy/genetics/metabolism/pathology
MH  - Pregnancy
MH  - Proteinuria/*drug therapy/genetics/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*antagonists & inhibitors/metabolism
MH  - Uterus/blood supply/drug effects/metabolism
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
MH  - Vascular Endothelial Growth Factor Receptor-1/*antagonists & 
      inhibitors/genetics/metabolism
OTO - NOTNLM
OT  - Angiogenic factors
OT  - Antioxidants
OT  - Hydrogen peroxide
OT  - Molecular hydrogen
OT  - Oxidative stress
OT  - Preeclampsia
EDAT- 2016/10/30 06:00
MHDA- 2017/12/30 06:00
CRDT- 2016/10/30 06:00
PHST- 2016/04/20 00:00 [received]
PHST- 2016/10/21 00:00 [revised]
PHST- 2016/10/21 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/12/30 06:00 [medline]
PHST- 2016/10/30 06:00 [entrez]
AID - S0891-5849(16)30978-9 [pii]
AID - 10.1016/j.freeradbiomed.2016.10.491 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2016 Dec;101:524-533. doi: 
      10.1016/j.freeradbiomed.2016.10.491. Epub 2016 Oct 24.