# Hydrogen-rich medium protects mouse embryonic fibroblasts from oxidative stress by activating LKB1-AMPK-FoxO1 signal pathway.
> 水素リッチ培地はLKB1-AMPK-FoxO1シグナル経路の活性化を介してマウス胚性線維芽細胞を酸化ストレスから保護する


## Abstract

This in vitro study investigated how hydrogen-rich medium influences intracellular signaling in mouse embryonic fibroblasts (MEFs). Exposure to hydrogen-rich medium activated the LKB1-AMPK signaling cascade independently of ATP depletion, subsequently driving FoxO1-mediated transcriptional upregulation of manganese superoxide dismutase and catalase. When MEFs were challenged with hydrogen peroxide, hydrogen-rich medium markedly reduced intracellular reactive oxygen species accumulation and suppressed apoptosis through an AMPK-dependent mechanism. These findings identify the LKB1-AMPK-FoxO1 axis as a key mediator of the antioxidant capacity of molecular hydrogen, supporting a role for H2 as a signaling molecule capable of modulating cellular energy and redox homeostasis beyond simple radical scavenging.

### Mechanism

Hydrogen-rich medium activates LKB1-AMPK without depleting ATP, which triggers FoxO1-dependent transcription of manganese superoxide dismutase and catalase, thereby reducing ROS levels and inhibiting apoptosis in an AMPK-dependent manner.

## Bibliographic

- **Authors**: Lee J, Yang G, Kim YJ, Tran QH, Choe W, Kang I, et al.
- **Journal**: Biochem Biophys Res Commun
- **Year**: 2017 (2017-09-23)
- **PMID**: [28743498](https://pubmed.ncbi.nlm.nih.gov/28743498/)
- **DOI**: [10.1016/j.bbrc.2017.07.119](https://doi.org/10.1016/j.bbrc.2017.07.119)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive

## 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)

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> **Cite as**: H2 Papers — PMID 28743498. https://h2-papers.org/en/papers/28743498
> **Source**: PubMed PMID [28743498](https://pubmed.ncbi.nlm.nih.gov/28743498/)