# Intake of Molecular Hydrogen in Drinking Water Increases Membrane Transporters,-Glycoprotein, and Multidrug Resistance-Associated Protein 2 without Affecting Xenobiotic-Metabolizing Enzymes in Rat Liver.
> 水素水摂取がラット肝臓のP糖タンパク質およびMrp2発現を増加させる一方で薬物代謝酵素には影響しないことの検討


## Abstract

This animal study examined the effects of four-week ad libitum hydrogen-rich water (HRW) intake on hepatic xenobiotic metabolism, membrane transporter expression, and oxidative stress markers in rats. HRW was generated using hybrid magnesium-carbon hydrogen storage materials. Activities of multiple cytochrome P450 isoforms (CYP1A1, 1A2, 2B, 2C, 2D, 2E1, 3A, 4A), glutathione S-transferase, and UDP-glucuronosyltransferase remained unchanged. Plasma biochemical parameters were largely unaffected, with only a mild reduction in glucose concentration observed. Hepatic glutathione content, glutathione peroxidase activity, and lipid peroxidation levels showed no significant differences from controls. Notably, protein expression of P-glycoprotein and multidrug resistance-associated protein 2 (Mrp2) was elevated in liver tissue, suggesting that HRW may enhance biliary efflux of xenobiotics and potentially toxic compounds without disrupting phase I or phase II metabolic pathways.

### Mechanism

HRW intake upregulated hepatic P-glycoprotein and Mrp2 protein expression, potentially enhancing biliary efflux of xenobiotics and toxic substances. No changes were detected in cytochrome P450 enzyme activities, phase II conjugation enzymes, glutathione levels, or lipid peroxidation markers.

## Bibliographic

- **Authors**: Yao HT, Yang Y, Li M
- **Journal**: Molecules
- **Year**: 2019 (2019-07-19)
- **PMID**: [31330936](https://pubmed.ncbi.nlm.nih.gov/31330936/)
- **DOI**: [10.3390/molecules24142627](https://doi.org/10.3390/molecules24142627)
- **PMC**: [PMC6680492](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680492/)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: mixed

## 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 31330936. https://h2-papers.org/en/papers/31330936
> **Source**: PubMed PMID [31330936](https://pubmed.ncbi.nlm.nih.gov/31330936/)