Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats

Abstract

Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFa and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 h decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD.

Study details

Article type

Original Research

Disease / injury model

Bronchopulmonary dysplasia (BPD) induced by intra-amniotic LPS injection

Duration

19 days

Dose comparison

Hydrogen water was administered at a supersaturated concentration (5-7 ppm) compared to dehydrogenized water; hydrogen concentration in milk was ~0.5 ppm.

Dose-dependent effect

No

Outcome

Positive

Findings

Hydrogen-rich water administered to pregnant rats ameliorated LPS-induced bronchopulmonary dysplasia in newborn rats by normalizing alveolar enlargement, reducing oxidative stress markers (nitrotyrosine, 8-OHdG), restoring gene expression of FGFR4, VEGFR2, and HO-1, and suppressing inflammatory proteins TNFa and IL-6. No adverse effects were observed.