# The Combination of Molecular Hydrogen and Heme Oxygenase 1 Effectively Inhibits Neuropathy Caused by Paclitaxel in Mice.
> 分子状水素とヘムオキシゲナーゼ1の併用によるパクリタキセル誘発性末梢神経障害の抑制効果（マウスモデル）


## Abstract

This study investigated the combined effects of hydrogen-rich water (HRW) and the heme oxygenase-1 (HO-1) inducer cobalt protoporphyrin IX (CoPP) on paclitaxel (PTX)-induced peripheral neuropathy in male C57BL/6 mice. Low-dose co-administration produced faster and greater reductions in mechanical and thermal allodynia compared with either agent alone, and also suppressed anxiodepressive-like behaviors. In the amygdala and dorsal root ganglia, the combination attenuated NLRP3 inflammasome activation, 4-hydroxynonenal accumulation, and pro-inflammatory mediator mRNA levels. Concurrently, expression of NRF2, HO-1, superoxide dismutase 1, glutathione S-transferase mu 1, and glutamate-cysteine ligase modifier subunit was elevated, while BACH1 protein levels declined. These findings indicate a synergistic interaction between the HO-1 and H2 systems in modulating oxidative stress and inflammation associated with PTX-induced neuropathy.

### Mechanism

Co-administration of HRW and CoPP activates the NRF2 antioxidant pathway, upregulating HO-1, SOD1, and glutathione-related enzymes while reducing BACH1 protein and suppressing NLRP3 inflammasome activation and 4-hydroxynonenal accumulation in dorsal root ganglia and amygdala.

## Bibliographic

- **Authors**: Martínez-Martel I, Bai X, Kordikowski R, Leite-Panissi CRA, Pol O
- **Journal**: Antioxidants (Basel)
- **Year**: 2024 (2024-07-17)
- **PMID**: [39061924](https://pubmed.ncbi.nlm.nih.gov/39061924/)
- **DOI**: [10.3390/antiox13070856](https://doi.org/10.3390/antiox13070856)
- **PMC**: [PMC11274132](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11274132/)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; 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 39061924. https://h2-papers.org/en/papers/39061924
> **Source**: PubMed PMID [39061924](https://pubmed.ncbi.nlm.nih.gov/39061924/)