title: Molecular hydrogen ameliorates several characteristics of preeclampsia in the Reduced Uterine Perfusion Pressure (RUPP) rat model.
abstract: Oxidative stress plays an important role in the pathogenesis of preeclampsia. Recently, molecular hydrogen (H2) has been shown to have therapeutic potential in various oxidative stress-related diseases. The aim of this study is to investigate the effect of H2on preeclampsia. We used the reduced utero-placental perfusion pressure (RUPP) rat model, which has been widely used as a model of preeclampsia. H2water (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 H2on placental villi were examined by using a trophoblast cell line (BeWo) and villous explants from the placental tissue of women with or without preeclampsia. H2significantly attenuated hydrogen peroxide-induced sFlt-1 expression, but could not reduce the expression induced by hypoxia in BeWo cells. H2significantly attenuated sFlt-1 expression in villous explants from women with preeclampsia, but not affected them from normotensive pregnancy. The prophylactic administration of H2attenuated placental ischemia-induced hypertension, angiogenic imbalance, and oxidative stress. These results support the theory that H2has a potential benefit in the prevention of preeclampsia.
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Takafumi
authors: T
authors: Ushida
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: itoto@med.nagoya-u.ac.jp.
authors: Tomomi
authors: T
authors: Kotani
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Hiroyuki
authors: H
authors: Tsuda
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Kenji
authors: K
authors: Imai
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Tomoko
authors: T
authors: Nakano
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Shima
authors: S
authors: Hirako
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Yumiko
authors: Y
authors: Ito
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Hua
authors: H
authors: Li
authors: Mano Women's Clinic, 2-5 Matsushin-cho, Kasugai city, Aichi Prefecture 486-0931, Japan.
authors: Yukio
authors: Y
authors: Mano
authors: Laboratory of Bell Research Center-Department of Obstetrics and Gynaecology Collaborative Research, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Jingwen
authors: J
authors: Wang
authors: Laboratory of Bell Research Center-Department of Obstetrics and Gynaecology Collaborative Research, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Rika
authors: R
authors: Miki
authors: Department of Healthcare Administration, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Eiko
authors: E
authors: Yamamoto
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Akira
authors: A
authors: Iwase
authors: Department of Cardiology, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Yasuko K
authors: YK
authors: Bando
authors: Division of Neurogenetics, Center for Neurological Diseases and Cancer, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Masaaki
authors: M
authors: Hirayama
authors: Division of Neurogenetics, Center for Neurological Diseases and Cancer, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Kinji
authors: K
authors: Ohno
authors: Department of Pathology and Biological Responses, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Shinya
authors: S
authors: Toyokuni
authors: Department of Gynecology and Obstetrics, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Fumitaka
authors: F
authors: Kikkawa
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D006859:Hydrogen / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011507:Proteinuria / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014599:Uterus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D006859:Hydrogen; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenic factors; Antioxidants; Hydrogen peroxide; Molecular hydrogen; Oxidative stress; Preeclampsia