Protective effects of hydrogen gas against sepsis-induced acute lung injury via regulation of mitochondrial function and dynamics

Dong, Aili; Yu, Yang; Wang, Yanyan; Li, Can; Chen, Hongguang; Bian, Yingxue; Zhang, Peng; Zhao, Yungang; Yu, Yonghao; Xie, Keliang

doi:10.1016/j.intimp.2018.10.012

Cited by 47 publications

(37 citation statements)

References 26 publications

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“…is transfer yields an electrochemical gradient that drives the synthesis of ATP and provides a central criterion for the assessment of the MMP, a marker of mitochondrial function [15,27]. e actions of noxious xenobiotic substances can directly or indirectly affect mitochondrial function, and such substances often disrupt various mitochondrial macromolecules and thus reduce the MMP, which in turn compromises several mitochondrial functions [15,27].…”

Section: Discussionmentioning

confidence: 99%

“…e fundamental mechanism underlying these positive effects has yet to be elucidated. A previous study found that H 2 enhanced the expression and activity of HO-1 both in vivo and in vitro [14,15]. Another study demonstrated that inhalation of 2% H 2 could potentially alleviate intestinal damage caused by severe sepsis by regulating the release of HO-1 and high mobility group box 1 (HMGB1) [16].…”

Section: Introductionmentioning

confidence: 99%

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[Retracted] Protective Effects of Hydrogen on Myocardial Mitochondrial Functions in Septic Mice

Zhang

Dong

Xie

et al. 2020

BioMed Research International

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Enhancement of mitochondrial physiological function prevents sepsis-induced dysfunction. The present study aimed to elucidate the mechanism by which hydrogen (H2) affects mitochondrial function in a wild-type (WT) and homozygous nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (KO, Nrf2−/−) murine model of sepsis. In myocardial tissues with severe sepsis, H2 gas treatment reduced mitochondrial dysfunction, whereas zinc protoporphyrin (ZnPPIX) negated these beneficial effects. H2 treatment upregulated the protein expression of mitofusin-2 (Mfn2), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), and protein heme oxygenase-1 (HO-1) in WT mice with severe sepsis but not in their Nrf2−/− counterparts, and this upregulation was inhibited in the presence of ZnPPIX. In conclusion, the mechanism by which H2 limits organ damage in mice with severe sepsis involves HO-1, whereas the mechanism that limits severe sepsis-related mitochondrial dysfunction involves both HO-1 and Nrf2.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

[Retracted] Protective Effects of Hydrogen on Myocardial Mitochondrial Functions in Septic Mice

Zhang

Dong

Xie

et al. 2020

BioMed Research International

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“…Second, hydrogen may induce the expression of some antioxidant enzymes that can eliminate ROS, and it plays key roles in regulating redox homeostasis of cancer cells (42, 47). Studies have indicated that upon hydrogen gas treatment, the expression of superoxide dismutase (SOD) (48), heme oxyganase-1 (HO-1) (49), as well as nuclear factor erythroid 2-related factor 2 (Nrf2) (50), increased significantly, strengthening its potential in eliminating ROS.…”

Section: Hydrogen Gas Selectively Scavenges Hydroxyl Radical and Peromentioning

confidence: 99%

Hydrogen Gas in Cancer Treatment

Liao

Sheng

et al. 2019

Front. Oncol.

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Gas signaling molecules (GSMs), composed of oxygen, carbon monoxide, nitric oxide, hydrogen sulfide, etc., play critical roles in regulating signal transduction and cellular homeostasis. Interestingly, through various administrations, these molecules also exhibit potential in cancer treatment. Recently, hydrogen gas (formula: H 2 ) emerges as another GSM which possesses multiple bioactivities, including anti-inflammation, anti-reactive oxygen species, and anti-cancer. Growing evidence has shown that hydrogen gas can either alleviate the side effects caused by conventional chemotherapeutics, or suppress the growth of cancer cells and xenograft tumor, suggesting its broad potent application in clinical therapy. In the current review, we summarize these studies and discuss the underlying mechanisms. The application of hydrogen gas in cancer treatment is still in its nascent stage, further mechanistic study and the development of portable instruments are warranted.

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“…11,12 H 2 is the lightest chemical element and can easily diffuse through membranes into cytosol and organelles, exerting anti-oxidation, anti-inflammation, and anti-apoptotic effects. 13,14 Under physiological conditions, breathing low concentrations of H 2 has been proven to be relatively safe, but as it has explosive property, the use of H 2 is limited in clinical practice. 15 In studies, H 2 is often dissolved in a solvent like physiological saline (hydrogen-rich saline, HRS) under high pressure to observe its effects in the treatment and prevention of diseases.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

Wang

Zhang

et al. 2019

Exp Biol Med (Maywood)

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Over-activation of autophagy due to increased levels of reactive oxygen species is a key mechanism of lipopolysaccharide-induced acute lung injury. Hydrogen-rich saline, an antioxidant, has been proved to be an effective agent for the prevention of acute lung injury, but the underlying mechanism remains unclear. Here, we investigated the mechanism through which hydrogen-rich saline prevents acute lung injury by focusing on autophagy regulation. The acute lung injury model was induced using lipopolysaccharide both in vivo and in vitro. The activation of autophagy was observed by detecting the expression of autophagy-related proteins using Western blotting. Lung histopathological changes, malondialdehyde content, wet/dry ratio, inflammatory cell count, protein content in bronchoalveolar lavage fluid, and cell viability were measured to evaluate the severity of acute lung injury. Intracellular reactive oxygen species levels were detected using dihydroethidium, which is a reactive oxygen species fluorescent probe. The results showed that the expression of Beclin-1 and microtubule-associated protein 1 light chain 3 II/I (LC3II/I ratio) was obviously increased after lipopolysaccharide administration. Pretreatment with hydrogen-rich saline markedly inhibited the expression of Beclin-1 and the LC3II/I ratio; ameliorated lung histopathological changes, malondialdehyde content and wet/dry ratio; and reduced protein content and infiltration of inflammatory cells in bronchoalveolar lavage fluid. These protective effects were also observed by pretreatment with autophagy inhibitor 3-methyladenine. Similar results were found in vitro. The production of reactive oxygen species and the activation of the AMPK/mTOR pathway were notably enhanced in MLE-12 cells after lipopolysaccharide treatment, and ameliorated by the hydrogen-rich medium. The activation of AMPK induced by lipopolysaccharide was also inhibited by pretreatment with N-acetyl-L-cysteine (a reactive oxygen species scavenger). In addition, the over-activation of autophagy was also suppressed by compound C (an AMPK inhibitor). In conclusion, hydrogen-rich saline alleviated lipopolysaccharide-induced acute lung injury by inhibiting excessive autophagy activation via the ROS/AMPK/mTOR pathway in mice. Hydrogen-rich saline may be a new therapeutic strategy for acute lung injury prevention and treatment in the future. Impact statement Acute lung injury (ALI), a common complication of many serious health issues, such as serious infection, burns, and shock, is one of the most common critical illnesses in clinical practice with a high mortality rate of 30–40%. There are still short of effective prevention and treatment measures. Evidence is growing that hydrogen-rich saline (HRS) may be an effective drug for the prevention and treatment of ALI. However, the mechanisms involved in have not been clearly understood. In this study, we investigated the underling mechanisms by focusing on autophagy regulation. The results showed that HRS ameliorated lipopolysaccharide-induced ALI in mice by inhibiting autophagy over-activation through ROS/AMPK/mTOR pathway. HRS may be a new therapeutic strategy for ALI prevention and treatment in the future.

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Protective effects of hydrogen gas against sepsis-induced acute lung injury via regulation of mitochondrial function and dynamics

Cited by 47 publications

References 26 publications

[Retracted] Protective Effects of Hydrogen on Myocardial Mitochondrial Functions in Septic Mice

[Retracted] Protective Effects of Hydrogen on Myocardial Mitochondrial Functions in Septic Mice

Hydrogen Gas in Cancer Treatment

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

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