# Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury.
> 水素ガスによるCaco-2細胞の虚血再灌流障害後ミトコンドリア膜電位および呼吸機能の回復促進


## Abstract

Using Caco-2 intestinal epithelial cells as an in vitro ischemia-reperfusion (I/R) model, this study examined how hydrogen-rich gas (99% H2, 1% O2) affects mitochondrial function after hypoxic exposure of 3, 6, or 24 hours followed by reoxygenation. Compared with nitrogen-based hypoxia controls, hydrogen-treated cells showed marked improvements in mitochondrial membrane potential, oxygen consumption rate, and ATP production during the reperfusion phase. Reactive oxygen species levels were reduced, and pro-apoptotic signaling was suppressed. Notably, expression of HIF1α and PDK1 was downregulated in hydrogen-exposed cells, indicating that molecular hydrogen may act upstream of hypoxia-driven metabolic reprogramming. These findings suggest that hydrogen supports oxidative phosphorylation and overall cellular energy metabolism under I/R conditions, providing mechanistic insight relevant to intestinal and other hypoxia-related pathologies.

### Mechanism

Molecular hydrogen downregulates HIF1α and PDK1 expression, thereby modulating hypoxia-driven signaling upstream. This promotes oxidative phosphorylation, restores mitochondrial membrane potential and ATP production, improves oxygen consumption, and reduces reactive oxygen species in I/R-injured intestinal cells.

## Bibliographic

- **Authors**: Seya M, Aokage T, Meng Y, Hirayama T, Obara T, Nojima T, et al.
- **Journal**: Biochem Biophys Res Commun
- **Year**: 2025 (2025-10-30)
- **PMID**: [41043278](https://pubmed.ncbi.nlm.nih.gov/41043278/)
- **DOI**: [10.1016/j.bbrc.2025.152753](https://doi.org/10.1016/j.bbrc.2025.152753)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive
- **H2 concentration**: 99%

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices 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)

---

> **Cite as**: H2 Papers — PMID 41043278. https://h2-papers.org/en/papers/41043278
> **Source**: PubMed PMID [41043278](https://pubmed.ncbi.nlm.nih.gov/41043278/)