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Hydrogen gas therapy attenuate inflammatory pathway signaling in septic mice

ABSTRACT: Molecular hydrogen (H2) has been used in several clinical cases. However, few studies have been reported on the use of hydrogen therapy for treatment of sepsis, and the anti-inflammatory mechanism of H2 remains majorly unknown. The aim of this study is to confirm the effects of H2 therapy for sepsis and reveal its therapeutic mechanism by performing RNA-seq in multiple organs in the septic mice. Nine-week-old C57BL/6 male mice underwent cecal ligation and puncture procedure (CLP) or sham procedure. Subsequently, the CLP model received an immediate +/- continuous inhalation of 7% H2. The H2 gas-treated groups were housed in the same cage, and they were put in a designated box that was able to maintain the concentration of H2 through constant H2 supply by a gas generator. Mice were observed for a week to assess their survival rates. Serum inflammatory cytokines were evaluated with ELISA at 24 h after the CLP procedure.

ORGANISM(S): Mus musculus

PROVIDER: GSE152527 | GEO | 2021/02/28

REPOSITORIES: GEO

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Project description:Background: The global demand for affordable carbon has never been stronger, and there is an imperative in many industrial processes to use waste streams to make products. Gas-fermenting acetogens offer a potential solution and several commercial gas fermentation plants are currently under construction. As energy limits acetogen metabolism, supply of H2 should diminish substrate loss to CO2 and facilitate production of reduced and energy-intensive products. However, the effects of H2 supply on CO-grown acetogens have yet to be experimentally quantified under controlled growth conditions. Results: Here, we quantify the effects of H2 supplementation by comparing growth on CO, syngas, and a high-H2 CO gas mix using chemostat cultures of Clostridium autoethanogenum. Cultures were characterised at the molecular level using metabolomics, proteomics, gas analysis, and a genome-scale metabolic model (GEM). CO-limited chemostats operated at two steady-state biomass concentrations facilitated co-utilisation of CO and H2. We show that H2 supply strongly impacts carbon distribution with a four-fold reduction in substrate loss as CO2 (61% vs. 17%) and a proportional increase of flux to ethanol (15% vs. 61%). Notably, H2 supplementation lowers the molar acetate/ethanol ratio by five-fold. At the molecular level, quantitative proteome analysis showed no obvious changes leading to these metabolic rearrangements suggesting the involvement of post-translational regulation. Metabolic modelling showed that H2 availability provided reducing power via H2 oxidation and saved redox as cells reduced all the CO2 to formate directly using H2 in the Wood-Ljungdahl pathway. Modelling further indicated that the methylene-THF reductase reaction was ferredoxin-reducing under all conditions. In combination with proteomics, modelling also showed that ethanol was synthesised through the acetaldehyde:ferredoxin oxidoreductase (AOR) activity. Conclusions: Our quantitative molecular analysis revealed that H2 drives rearrangements at several layers of metabolism and provides novel links between carbon, energy, and redox metabolism advancing our understanding of energy conservation in acetogens. We conclude that H2 supply can substantially increase the efficiency of gas fermentation and thus the feed gas composition can be considered an important factor in developing gas fermentation-based bioprocesses.

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Hydrogen gas therapy attenuate inflammatory pathway signaling in septic mice

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