# Preventing Cisplatin-Induced Neuropathy and Related Emotional Disorders with the Coadministration of Duloxetine and Hydrogen-Rich Water in Male and Female Mice.
> シスプラチン誘発性末梢神経障害および情動障害に対するデュロキセチンと水素水の併用効果：雌雄マウスを用いた検討


## Abstract

This study investigated the prophylactic effects of combining low-dose duloxetine (DULO) with hydrogen-rich water (HRW) in C57BL/6 male and female mice subjected to cisplatin (CIS)-induced peripheral neuropathy. The combined regimen outperformed either agent alone in preventing mechanical allodynia in both sexes and fully blocked cold allodynia in males, while only partially reducing it in females. Muscle strength deficits were prevented in both sexes by the combination. Anxiety- and depressive-like behaviors induced by CIS were ameliorated across all treatment groups, whereas body weight loss was not fully restored. Mechanistic analysis of dorsal root ganglia indicated that suppression of oxidative stress, inflammatory signaling, and neuroplasticity alterations may underlie the observed benefits. Sex-dependent differences in treatment response were also identified, highlighting the importance of biological sex as a variable in neuropathy research.

### Mechanism

The combination of duloxetine and hydrogen-rich water is proposed to prevent cisplatin-induced allodynia and muscle deficits by suppressing oxidative stress, inflammatory responses, and neuroplasticity alterations in the dorsal root ganglia.

## Bibliographic

- **Authors**: Martínez-Martel I, Negrini-Ferrari SE, Pol O
- **Journal**: Antioxidants (Basel)
- **Year**: 2025 (2025-08-16)
- **PMID**: [40867900](https://pubmed.ncbi.nlm.nih.gov/40867900/)
- **DOI**: [10.3390/antiox14081004](https://doi.org/10.3390/antiox14081004)
- **PMC**: [PMC12383221](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383221/)
- **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 40867900. https://h2-papers.org/en/papers/40867900
> **Source**: PubMed PMID [40867900](https://pubmed.ncbi.nlm.nih.gov/40867900/)