Int J Mol Sci

. 2021 Aug 31;22(17):9500. doi: 10.3390/ijms22179500. https://pubmed.ncbi.nlm.nih.gov/34502408/

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

Mayo Miura ¹, Kenji Imai ¹, Hiroyuki Tsuda ², Rika Miki ³, Sho Tano ¹, Yumiko Ito ², Shima Hirako-Takamura ⁴, Yoshinori Moriyama ⁵, Takafumi Ushida ¹, Yukako Iitani ¹, Tomoko Nakano-Kobayashi ¹, Shinya Toyokuni ⁶, Hiroaki Kajiyama ¹, Tomomi Kotani ^1 7Affiliations expand

• PMID: 34502408
• PMCID: PMC8431162
• DOI: 10.3390/ijms22179500

Free PMC article

Abstract

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, pO_2, 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.

Keywords: congenital diaphragmatic hernia; oxidative stress; platelet-derived growth factor.