Combination therapy of molecular hydrogen and hyperoxia improves survival rate and organ damage in a zymosan-induced generalized inflammation model
Hong Y, Sun L, Sun R, Chen H, Yu Y, Xie K. · Experimental and Therapeutic Medicine. 2016;11(6):2590-2596.
Study at a glance
Preclinical
Male ICR mice aged 6-8 weeks in a zymosan-induced generalized-inflammation and multiple-organ-damage model.
Two three-hour chamber exposures beginning one and six hours after zymosan. Groups received room air, 2% H₂ with 21% O₂, 98% O₂ alone, or 2% H₂ with 98% O₂. · The source reports a total chamber inflow of 4 L/min. Thus the H₂ flow was 80 mL/min in both H₂ conditions. O₂ flow was 840 mL/min with 21% O₂ and 3,920 mL/min with 98% O₂; these are direct calculations from the reported total flow and compositions.
Two three-hour exposures on the first day; organ outcomes at 24 hours and survival followed for 14 days.
Survival after zymosan was 20% with room air, 70% with 2% H₂, 60% with 98% O₂ and 100% with the combined mixture. H₂ and hyperoxia each attenuated organ-injury and inflammatory/oxidative measures, with larger reported effects in combination. H₂ did not materially alter PaO₂, and arterial pH and PaCO₂ did not differ among groups.
Preclinical sterile-inflammation model, two short exposures, small n=6 organ-outcome groups, many surrogate comparisons and an extreme 98% O₂ condition. The article reports Chinese national, Tianjin and public-health grants; no explicit conflict statement was identified, so absence is not inferred.
What kind of evidence is this?
Preclinical
Randomized six-group controlled mouse experiment with separate survival and 24-hour organ-injury cohorts
Critical care and ischemia-reperfusion
Inhaled H₂
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
Male ICR mice aged 6-8 weeks in a zymosan-induced generalized-inflammation and multiple-organ-damage model.
216 mice: 180 randomized to six groups of n=30 for 14-day survival and blood-gas assessment, plus 36 assigned to the same six groups of n=6 for 24-hour biochemical and histological outcomes.
Two three-hour exposures on the first day; organ outcomes at 24 hours and survival followed for 14 days.
Two three-hour chamber exposures beginning one and six hours after zymosan. Groups received room air, 2% H₂ with 21% O₂, 98% O₂ alone, or 2% H₂ with 98% O₂.
Inhaled H₂/O₂/N₂ mixtures — not Brown's gas: neither the 2% H₂ + 21% O₂ mixture nor the 2% H₂ + 98% O₂ mixture has the 2:1 H₂:O₂ ratio.
The source reports a total chamber inflow of 4 L/min. Thus the H₂ flow was 80 mL/min in both H₂ conditions. O₂ flow was 840 mL/min with 21% O₂ and 3,920 mL/min with 98% O₂; these are direct calculations from the reported total flow and compositions.
80 mL/min.
840 mL/min in the 21% O₂ mixture; 3,920 mL/min in the 98% O₂ mixture.
Normal-saline controls and zymosan-challenged mice exposed to room air, H₂ alone, hyperoxia alone, or the combined H₂/hyperoxia condition.
Outcomes and reported result
Fourteen-day survival, arterial blood gases, lung/liver/kidney histology, ALT, AST, creatinine, BUN, SOD, 8-iso-PGF2α, TNF-α and HMGB1.
Survival after zymosan was 20% with room air, 70% with 2% H₂, 60% with 98% O₂ and 100% with the combined mixture. H₂ and hyperoxia each attenuated organ-injury and inflammatory/oxidative measures, with larger reported effects in combination. H₂ did not materially alter PaO₂, and arterial pH and PaCO₂ did not differ among groups.
The complete free PMC article was checked for allocation, both cohorts, exact gas compositions and total flow, directly calculated H₂/O₂ flows, timing, survival and organ outcomes, null blood-gas findings, funding and available disclosures.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Preclinical sterile-inflammation model, two short exposures, small n=6 organ-outcome groups, many surrogate comparisons and an extreme 98% O₂ condition. The article reports Chinese national, Tianjin and public-health grants; no explicit conflict statement was identified, so absence is not inferred.
Experimental zymosan inflammation in male mice; it does not establish treatment of human sepsis or multiple-organ dysfunction.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 27284352 · DOI: 10.3892/etm.2016.3231
Free full article in PubMed Central.
Complete PMC article and PubMed metadata; full-text extraction checked 9 August 2026.
10 August 2026
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