# Effect of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia.
> 低酸素下でメトホルミン投与糖尿病ラットにおける水素水の乳酸値への影響


## Abstract

This animal study examined how hydrogen-rich water affects lactate metabolism in diabetic Sprague-Dawley rats receiving metformin under hypoxic conditions. Thirty rats were allocated to five groups: normal diet, diabetes model (DM), DM plus metformin (DMM), DMM plus hypoxia (DMMH), and DMMH plus hydrogen-rich water (DMMHR). Blood concentrations of lactic acid, pyruvate, and lactate dehydrogenase were significantly lower in the DMMHR group than in the DMMH group. In liver and heart tissues, superoxide dismutase and glutathione levels rose following hydrogen-rich water administration, while malondialdehyde and oxidized glutathione declined, indicating reduced oxidative stress. qPCR showed that pro-apoptotic genes Bax and Caspase-3 were upregulated in DM rats and suppressed by metformin; hypoxia reversed this suppression, and hydrogen-rich water had minimal effect on these genes under hypoxic conditions. Histological analysis revealed that hydrogen-rich water attenuated myocardial fiber damage. Overall, hydrogen-rich water reduced lactate accumulation and oxidative stress, and protected cardiac tissue in this diabetic hypoxia model.

### Mechanism

Hydrogen-rich water is proposed to scavenge reactive oxygen species, thereby elevating superoxide dismutase and glutathione while suppressing lipid peroxidation (malondialdehyde). This antioxidant action is associated with reduced lactate dehydrogenase activity, lower blood lactate and pyruvate, and attenuation of hypoxia-induced myocardial fiber damage in diabetic rats.

## Bibliographic

- **Authors**: Zhao C, Guo Y, Wang R, Cheng C, Chen X
- **Journal**: Korean J Physiol Pharmacol
- **Year**: 2021 (2021-11-01)
- **PMID**: [34697262](https://pubmed.ncbi.nlm.nih.gov/34697262/)
- **DOI**: [10.4196/kjpp.2021.25.6.517](https://doi.org/10.4196/kjpp.2021.25.6.517)
- **PMC**: [PMC8552820](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552820/)
- **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 34697262. https://h2-papers.org/en/papers/34697262
> **Source**: PubMed PMID [34697262](https://pubmed.ncbi.nlm.nih.gov/34697262/)