Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia

Hiroaki Kajiyama, Hiroyuki Tsuda, Kenji Imai, Mayo Miura, Rika Miki, Shima Hirako-Takamura, Shinya Toyokuni, Sho Tano, Takafumi Ushida, Tomoko Nakano-Kobayashi, Tomomi Kotani, Yoshinori Moriyama, Yukako Iitani, Yumiko Ito

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DOI: 10.3390/ijms22179500 DOI is the universal ID for this study.

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Oxidative stress plays a pathological role in pulmonary hypoplasia and pulmonary hypertension in congenital diaphragmatic hernia (CDH). This study investigated the effect of molecular hydrogen (H2), an antioxidant, on CDH pathology induced by nitrofen. Sprague-Dawley rats were divided into three groups: control, CDH, and CDH + hydrogen-rich water (HW). Pregnant dams of CDH + HW pups were orally administered HW from embryonic day 10 until parturition. Gasometric evaluation and histological, immunohistochemical, and real-time polymerase chain reaction analyses were performed. Gasometric results (pH, pO2, and pCO2 levels) were better in the CDH + HW group than in the CDH group. The CDH + HW group showed amelioration of alveolarization and pulmonary artery remodeling compared with the CDH group. Oxidative stress (8-hydroxy-2'-deoxyguanosine-positive-cell score) in the pulmonary arteries and mRNA levels of protein-containing pulmonary surfactant that protects against pulmonary collapse (surfactant protein A) were significantly attenuated in the CDH + HW group compared with the CDH group. Overall, prenatal H2 administration improved respiratory function by attenuating lung morphology and pulmonary artery thickening in CDH rat models. Thus, H2 administration in pregnant women with diagnosed fetal CDH might be a novel antenatal intervention strategy to reduce newborn mortality due to CDH.

Publish Year 2021
Country Japan
Rank Positive
Journal International Journal of Molecular Sciences
Primary Topic Pregnancy
Secondary TopicEnvironmental Pollution
Model Rat
Tertiary TopicHerbicide Toxicity (Nitrofen)
Vehicle Water (Electrolysis)
pH Neutral
Application Ingestion