# Molecular Hydrogen Attenuated N-methyl-N-Nitrosourea Induced Corneal Endothelial Injury by Upregulating Anti-Apoptotic Pathway.
> 水素分子はN-メチル-N-ニトロソウレア誘発角膜内皮障害において抗アポトーシス経路を活性化することで保護効果を示す


## Abstract

This study examined the impact of molecular hydrogen (H2) on corneal endothelial cell (CEC) damage induced by N-methyl-N-nitrosourea (MNU) and the associated mechanisms. In animal models, hydrogen-rich saline (HRS) was applied topically for 14 days, with immunofluorescence, immunohistochemical staining, and corneal endothelial assessments used to evaluate structural and cellular changes. MNU suppressed CEC proliferation and physiological function by promoting apoptosis and reducing ZO-1 and Na+/K+-ATPase expression. H2 counteracted these effects by inhibiting apoptosis. Cell-based experiments further revealed that H2 reversed MNU-induced damage through reduction of oxidative stress and modulation of both the NF-κB/NLRP3 and FOXO3a/p53/p21 signaling pathways. These findings indicate that topical H2 application can preserve corneal endothelial integrity and reduce the incidence and severity of corneal endothelial decompensation.

### Mechanism

H2 reduces oxidative stress and suppresses both the NF-κB/NLRP3 and FOXO3a/p53/p21 signaling pathways, thereby inhibiting apoptosis and preserving CEC proliferation along with ZO-1 and Na+/K+-ATPase expression.

## Bibliographic

- **Authors**: Li R, Qu Y, Li XM, Tao Y, Yang QQ, Wang J, et al.
- **Journal**: Invest Ophthalmol Vis Sci
- **Year**: 2021 (2021-07-01)
- **PMID**: [34196654](https://pubmed.ncbi.nlm.nih.gov/34196654/)
- **DOI**: [10.1167/iovs.62.9.2](https://doi.org/10.1167/iovs.62.9.2)
- **PMC**: [PMC8267183](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267183/)
- **Study type**: animal study
- **Delivery route**: mixed routes
- **Effect reported**: positive

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 34196654. https://h2-papers.org/en/papers/34196654
> **Source**: PubMed PMID [34196654](https://pubmed.ncbi.nlm.nih.gov/34196654/)