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, 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.
Highlights
Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a mortality rate as high as 20–40% [1,2]
Group was significantly lower than that in the control group (p < 0.01, Figure 1a), and the lung weight to body weight (LW/BW) ratio did not improve in the congenital diaphragmatic hernia (CDH) + hydrogen-rich water (HW) group (Figure 1a)
H2 was found to suppress 8-OHdG-positive cells in the pulmonary arterial walls, which is consistent with the results of the present study. These findings suggest that a reduction of oxidative stress could improve pulmonary hypertension (PH) by attenuating pulmonary remodeling in CDH
Summary
Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a mortality rate as high as 20–40% [1,2]. CDH presents a defect in the diaphragm through which the abdominal organs migrate into the thoracic cavity. Pulmonary growth is restricted by the compression of the migrated organs into the thoracic cavity during the fetal period. Extracorporeal membrane oxygenation (ECMO) has been used in patients with CDH who are unresponsive to optimal medication and ventilation. This therapeutic approach can only be used after birth. The pathology of PH in patients with CDH is characterized by an extensive muscularization of vessels and pulmonary vascular remodeling, which starts early during gestation [6]. We and others have reported the pathological role of oxidative stress in pulmonary hypoplasia and PH in CDH [10,11,12]
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