Preserved Acute Pulmonary Endothelial Homeostasis with Hydrogen Gas Inhalation After Neonatal Hypoxia-Ischemia Despite Increased Neutrophil Accumulation.
Takayuki Yokota, Masumi Iketani, Toui Tsuchiya, Kosuke Sakamoto, Yasuhiro Nakao, Tsutomu Mitsuie, Eri Inoue, Kota Inoue, Tomoaki Kusaka, Takayuki Wakabayashi, Kosuke Koyano, Takanori Miki, Masaki Ueno, Shinji Nakamura, Takashi Kusaka · Biomedicines · 2026
Research-use notice
Independent study record
Each H2HUBB study page organizes source-linked research details for educational use. Interpretation should remain proportional to the study design, population, controls, and limitations.
H2HUBB TAKEAWAY
In an animal model, although lung neutrophil counts were significantly higher in the HI-H₂ group, pulmonary gas exchange remained preserved, with no significant differences in arterial blood gases, oxygen index, or alveolar-arterial oxygen difference. H₂ inhalation did not increase pulmonary ICAM-1 expression or iNOS induction compared with untreated animals. The authors linked these findings to activation of the Nrf2/HO-1 pathway. These preclinical findings add evidence supporting molecular hydrogen's therapeutic potential within the outcomes and biological pathways measured in this model.
What the Findings Mean
H2HUBB reviewed how molecular hydrogen was evaluated in this publication and summarizes the source-grounded findings below. Although lung neutrophil counts were significantly higher in the HI-H₂ group, pulmonary gas exchange remained preserved, with no significant differences in arterial blood gases, oxygen index, or alveolar-arterial oxygen difference.
What the Researchers Studied
The study used a preclinical animal experiment. The comparison condition was control condition or baseline measurements.
What Effects Did Molecular Hydrogen Have?
Source-reported hydrogen concentration: 2.7% source-reported H₂ gas concentration; Source-reported hydrogen exposure: 2.7% source-reported H₂ gas concentration. Although lung neutrophil counts were significantly higher in the HI-H₂ group, pulmonary gas exchange remained preserved, with no significant differences in arterial blood gases, oxygen index, or alveolar-arterial oxygen difference. The authors concluded that H₂ inhalation preserved pulmonary endothelial homeostasis without impairing respiratory function during the acute phase after neonatal hypoxic-ischemic insult. These findings suggest that hydrogen did not impair pulmonary endothelial homeostasis and does not exacerbate redox-mediated inflammatory signaling in the early post-insult phase. Given that H₂ selectively scavenges hydroxyl radicals and peroxynitrite, it is plausible that hydrogen attenuates redox-dependent signaling pathways involved in endothelial activation, thereby preventing the amplification of inflammatory responses [ 16 ]. The authors linked these findings to activation of the Nrf2/HO-1 pathway.
Why These Findings Matter
These preclinical findings add evidence supporting molecular hydrogen's therapeutic potential within the outcomes and biological pathways measured in this model.
How Strong Is This Evidence?
This is preclinical animal evidence from a preclinical animal experiment. It is most informative for the disease model, mechanisms, biomarkers, and outcomes directly measured in the study.
Technical Study Details
H2HUBB classifies this publication as animal study with preclinical animal evidence. The reported sample size was 10. The study used a preclinical animal experiment. The source-reported hydrogen concentration was 2.7% source-reported H₂ gas concentration.
Limitations and Safety
Safety information: The observed increase in lung neutrophils was not accompanied by evidence of endothelial activation or deterioration of gas exchange, supporting the acute pulmonary safety of H₂ inhalation while suggesting that neutrophil accumulation may, at least in part, reflect hemodynamic redistribution rather than injurious inflammatory infiltration. direct assessment of pulmonary hemodynamics will be required to clarify the mechanisms underlying neutrophil redistribution and to further establish the pulmonary safety and therapeutic potential of H₂.
Original Study and H2HUBB Research Context
H2HUBB presents this source-grounded research record as one contribution to the broader molecular-hydrogen evidence base.