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Hydrogen-rich saline regulates NLRP3 inflammasome activation in sepsis-associated encephalopathy rat model.

水素富化生理食塩水による敗血症関連脳症ラットモデルにおけるNLRP3インフラマソーム活性化の調節

Abstract

Sepsis-associated encephalopathy (SAE) causes lasting cognitive and psychiatric sequelae in sepsis survivors. This study examined the neuroprotective potential of hydrogen-rich saline (HRS) in a juvenile rat SAE model induced by intraperitoneal lipopolysaccharide (LPS, 5 mg/kg). HRS (5 ml/kg) was administered 1 hour after LPS injection. Compared with untreated septic animals, HRS-treated rats exhibited reduced levels of pro-inflammatory cytokines TNF-α and IL-1β, elevated activities of antioxidant enzymes SOD, CAT, and GPX, and decreased MDA, MPO, and 8-OHdG levels. Immunofluorescence revealed fewer MMP-9- and NLRP3-positive cells, along with reduced GFAP, IBA-1, and CD86 immunoreactivity and increased CD206 expression. Western blot analysis demonstrated downregulation of NLRP3, ASC, caspase-1, MMP-2/9, TLR4, and Bax proteins, with concurrent upregulation of Bcl-2. These findings indicate that HRS suppresses neuroinflammation, NLRP3 inflammasome activation, neuronal apoptosis, and mitochondrial dysfunction through the NLRP3/Caspase-1/TLR4 signaling axis in juvenile SAE rats.

Mechanism

HRS suppresses NLRP3 inflammasome assembly and downstream caspase-1 activation via the NLRP3/Caspase-1/TLR4 signaling axis, while concurrently reducing oxidative stress markers and enhancing antioxidant enzyme activities, thereby attenuating neuroinflammation and neuronal apoptosis.

Bibliographic

Authors

Dumbuya JS, Chen X, Du J, Li SC, Liang L, Xie H, et al.

Journal

Int Immunopharmacol

Year

2023

PMID

37556997

DOI

10.1016/j.intimp.2023.110758

Tags

Delivery context

Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% devices are not recommended).

Safety notes

See also:

• Inhalation concentration and LFL / UFL
• Consumer Affairs Agency accident cases
• Inhalation safety threshold lineage

Other papers on the same disease / condition

• The protective effects of molecular hydrogen in sepsis-associated encephalopathy: current status.
  2026 ・ Eur J Pharmacol ・ mixed routes ・ not assessed
• Mitochondrial dysfunction, neuroinflammation, and associated mechanisms in sepsis-associated encephalopathy: from pathogenesis to emerging therapeutics.
  2026 ・ Front Neurosci ・ not specified ・ not assessed
• Effect of molecular hydrogen treatment on Sepsis-Associated encephalopathy in mice based on gut microbiota.
  2023 ・ CNS Neurosci Ther ・ mixed routes ・ positive
• Molecular hydrogen attenuates sepsis-induced cognitive dysfunction through regulation of tau phosphorylation.
  2023 ・ Int Immunopharmacol ・ inhalation ・ positive
• Inhaled molecular hydrogen reduces hippocampal neuroinflammation, glial reactivity and ameliorates memory impairment during systemic inflammation.
  2023 ・ Brain Behav Immun Health ・ inhalation ・ positive
• Emerging Trends and Hot Spots in Sepsis-Associated Encephalopathy Research From 2001 to 2021: A Bibliometric Analysis.
  2022 ・ Front Med (Lausanne) ・ not specified ・ not assessed
• Hydrogen Gas Alleviates Sepsis-Induced Brain Injury by Improving Mitochondrial Biogenesis Through the Activation of PGC-α in Mice.
  2021 ・ Shock ・ inhalation ・ positive
• Hydrogen gas alleviates sepsis-induced neuroinflammation and cognitive impairment through regulation of DNMT1 and DNMT3a-mediated BDNF promoter IV methylation in mice.
  2021 ・ Int Immunopharmacol ・ inhalation ・ positive