# Long-Term Consumption of Hydrogen-Rich Water Mitigates Oxidative Stress, Hepatic Inflammation, and Apoptosis in Rats with LPS-Induced Chronic Liver Injury

**Authors:** Luyao Zhang, Hanyu Wang, Yingxuan Mai, Qi He, Tao Liu, Na Zhang, Jiantao Zhang

PMC · DOI: 10.3390/antiox15020260 · Antioxidants · 2026-02-18

## TL;DR

Drinking hydrogen-rich water long-term may protect the liver from chronic inflammation and damage in rats.

## Contribution

This study demonstrates the long-term protective effects of hydrogen-rich water on chronic liver inflammation in rats.

## Key findings

- Long-term HRW consumption reduced inflammatory cell infiltration and pro-inflammatory factors in liver tissue.
- HRW suppressed apoptotic signaling pathways and preserved anti-apoptotic protein Bcl-2 in chronic inflammation.
- HRW may delay chronic liver injury by reducing oxidative stress, inflammation, and apoptosis.

## Abstract

(1) Background: Chronic inflammation is considered an important pathological basis underlying the development and progression of multiple metabolic liver diseases; although hydrogen-rich water (HRW) has shown beneficial effects in acute inflammation, its long-term impact on chronic hepatic inflammation remains unclear. (2) Methods: Sprague–Dawley rats were pretreated with HRW for 8 months, after which a lipopolysaccharide (LPS)-induced rat model of chronic hepatic inflammation was established, with continuous HRW administration throughout the experimental period. (3) Results: Long-term HRW consumption significantly reduced LPS-induced inflammatory cell infiltration in liver tissue, suppressed the abnormal elevation of pro-inflammatory factors, and maintained relatively stable expression levels of anti-inflammatory factors. In addition, HRW attenuated pro-apoptotic signaling associated with the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (including Bax, Cyt c, Caspase-3, Caspase-8, Caspase-9, Caspase-12, CHOP, and GRP78), while preserving the expression of the anti-apoptotic protein Bcl-2, thereby partially preventing the tendency toward hepatocyte apoptosis induced by chronic inflammation. (4) Conclusions: Long-term consumption of HRW may delay the onset and progression of chronic inflammation-related liver injury by alleviating inflammatory responses, oxidative stress, mitochondrial dysfunction, and apoptotic activity, thus exerting a preventive protective effect on the liver.

## Linked entities

- **Genes:** BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], CytC (mitochondrial cytochrome C) [NCBI Gene 408270], Casp3 (caspase 3) [NCBI Gene 12367], casp8 (caspase 8, apoptosis-related cysteine peptidase) [NCBI Gene 58022], Casp9 (caspase 9) [NCBI Gene 12371], Caspase-12 (caspase-12) [NCBI Gene 101725565], DDIT3 (DNA damage inducible transcript 3) [NCBI Gene 1649], HSPA5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 3309], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596]

## Full-text entities

- **Genes:** Mfn2 (mitofusin 2) [NCBI Gene 64476] {aka HSG}, Gpx1 (glutathione peroxidase 1) [NCBI Gene 24404] {aka GSHPx, GSHPx-1}, Opa1 (OPA1, mitochondrial dynamin like GTPase) [NCBI Gene 171116], Actb (actin, beta) [NCBI Gene 81822] {aka Actx}, Casp8 (caspase 8) [NCBI Gene 64044] {aka CASP-8}, Atf6 (activating transcription factor 6) [NCBI Gene 304962], Mfn1 (mitofusin 1) [NCBI Gene 192647] {aka Fzo1b}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, Casp12 (caspase 12) [NCBI Gene 156117], Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Ddit3 (DNA-damage inducible transcript 3) [NCBI Gene 29467] {aka CHOP, CHOP-10, Chop10, Gadd153, RM4}, Hspa5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 25617] {aka BIP, GRP 78, GRP78}, CYTB (cytochrome b) [NCBI Gene 26192], Pdlim3 (PDZ and LIM domain 3) [NCBI Gene 114108] {aka Actn2lp, Alp}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Crmp1 (collapsin response mediator protein 1) [NCBI Gene 25415], Fis1 (fission, mitochondrial 1) [NCBI Gene 288584] {aka Ttc11}, Tfam (transcription factor A, mitochondrial) [NCBI Gene 83474] {aka Mttfa}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}, Crp (C-reactive protein) [NCBI Gene 25419] {aka Aa1249, Ab1-341, Ab2-196, Ac1-114, Ac1262, Ac2-069}, ND1 (NADH dehydrogenase subunit 1) [NCBI Gene 26193], Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], Col1a1 (collagen type I alpha 1 chain) [NCBI Gene 29393] {aka COLIA1}, Nrf1 (nuclear respiratory factor 1) [NCBI Gene 312195] {aka Nfe2l1_retired}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Casp9 (caspase 9) [NCBI Gene 58918] {aka Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Tnfrsf1a (TNF receptor superfamily member 1A) [NCBI Gene 25625] {aka TNFR-1, Tnfr1}, ND4 (NADH dehydrogenase subunit 4) [NCBI Gene 26201]
- **Diseases:** colitis (MESH:D003092), hepatic functional failure (MESH:D017114), H (MESH:D000848), necrosis (MESH:D009336), tissue injury (MESH:D017695), chronic (MESH:D002908), hepatic pathological (MESH:D005598), hepatic injury (MESH:D056486), liver alterations (MESH:D017093), nonalcoholic steatohepatitis (MESH:D065626), HL (MESH:C000719624), liver fibrosis (MESH:D008103), Inflammation (MESH:D007249), chronic liver disease (MESH:D008107), Chronic Hepatic Inflammation (MESH:D006521), injury (MESH:D014947), cirrhosis (MESH:D005355), Mitochondrial Dysfunction (MESH:D028361), Metabolic Impairment (MESH:D008659), acute (MESH:D000208), Chronic Liver Injury (MESH:D056487)
- **Chemicals:** uranyl acetate (MESH:C005460), epoxy (MESH:D004853), aluminum (MESH:D000535), HRW (-), H&amp;E (MESH:D006371), hematoxylin (MESH:D006416), eosin (MESH:D004801), glutaraldehyde (MESH:D005976), LY (MESH:D008239), Hydrogen (MESH:D006859), DAPI (MESH:C007293), ROS (MESH:D017382), calcium (MESH:D002118), ATP (MESH:D000255), paraformaldehyde (MESH:C003043), lipid (MESH:D008055), LPS (MESH:D008070), nitrogen (MESH:D009584), MDA (MESH:D015104), paraffin (MESH:D010232), osmium tetroxide (MESH:D009993), NE (MESH:D009356), SDS (MESH:D012967), water (MESH:D014867), isoflurane (MESH:D007530), glycogen (MESH:D006003), TRIzol (MESH:C411644)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938009/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938009/full.md

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Source: https://tomesphere.com/paper/PMC12938009