# Suppression of ERK phosphorylation through oxidative stress is involved in the mechanism underlying sevoflurane-induced toxicity in the developing brain.
> セボフルラン誘発性発達脳毒性におけるERKリン酸化抑制と酸化ストレスの関与


## Abstract

Using neonatal mouse models, this study examined the causal role of ERK phosphorylation suppression in anesthetic-induced developmental neurotoxicity. At postnatal day 6 (P6), mice received either 2% sevoflurane or the MEK inhibitor SL327 (50 mg/kg, intraperitoneal). Both interventions produced comparable increases in neuronal apoptosis, whereas the same SL327 dose administered at P14 or P21 did not elicit apoptosis despite equivalent ERK inhibition. Administration of molecular hydrogen restored ERK phosphorylation and reduced sevoflurane-induced apoptotic cell death. These findings indicate that ERK phosphorylation suppression, mediated through oxidative stress, is a critical mechanistic component of sevoflurane neurotoxicity specifically during a vulnerable developmental window.

### Mechanism

Sevoflurane induces oxidative stress that suppresses ERK phosphorylation in the neonatal brain, triggering neuronal apoptosis. Molecular hydrogen restores ERK phosphorylation by scavenging reactive oxygen species, thereby reducing apoptotic cell death during the critical developmental period.

## Bibliographic

- **Authors**: Yufune S, Satoh Y, Akai R, Yoshinaga Y, Kobayashi Y, Endo S, et al.
- **Journal**: Sci Rep
- **Year**: 2016 (2016-02-24)
- **PMID**: [26905012](https://pubmed.ncbi.nlm.nih.gov/26905012/)
- **DOI**: [10.1038/srep21859](https://doi.org/10.1038/srep21859)
- **PMC**: [PMC4764822](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764822/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information 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)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 26905012. https://h2-papers.org/en/papers/26905012
> **Source**: PubMed PMID [26905012](https://pubmed.ncbi.nlm.nih.gov/26905012/)