Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression

Li, Qian; Hu, Liang; Li, Juan; Pan, Yu; Hu, Fan; Wan, Bing; Xu, Mengxia; Cheng, Huixian; Yu, Wenli; Jiang, Liang; Shi, Ya-dan; Li, Jincan; Duan, Manlin; Long, Yun; Li, Wentao

doi:10.3389/fimmu.2021.625957

Cited by 6 publications

(4 citation statements)

References 43 publications

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“…It inhibits NF-κB signaling pathway-mediated inflammation and apoptosis in the lung (Xie et al 2012), reduces p38 MAPK expression and inhibits p38 MAPK activation (Liang et al 2012), inhibits the RhoA mediated pathway (Yang et al 2016), and modulates autophagy through the mTOR/TFEB signaling pathway and the PINK1/Parkin mitophagy pathway (Fu et al 2020;Chen et al 2021). Recently, molecular hydrogen was found to activate thioredoxin 1 and decrease tissue factor expression, alleviating inflammatory and coagulation cascade reactions (Li et al 2021). Through these mechanisms, molecular hydrogen considerably improved the survival rate of mice with LPS and reduced lung edema and hemorrhage, inflammatory cell infiltration, and inflammatory cytokine secretion.…”

Section: Sepsis-induced Alimentioning

confidence: 99%

“…activating Nrf2/HO-1; improves mitochondrial function; decreases NLRP3 inflammasome through activating autophagy Inhibits NF-κB; inhibits p38 MAPK; inhibits RhoA; modulates mTOR/TFEB autophagy and PINK1/Parkin mitophagy; activates thioredoxin 1 and decreases tissue factor expressionXie et al (2010Xie et al ( , 2012,Liang et al (2012),Li et al (2015Li et al ( , 2021,Yang et al (2016),Dong et al (2018),Chen et al (2019Chen et al ( , 2021, Yu et al (2019), Fu et al (2020) COVID-19 Inhibits MCP-1, IL-6, IL-1β; inhibits NLRP3 pathway, modulates Nrf2 signaling pathway Chen et al (2019), Niu et al (2020), Wang et al (2020) I/R induced ALI Induces HO-1, inhibits p38 MAPK and NF-κB, decreases IL-8, IL-1β, TNF-α; inhibits apoptosis and pyroptosis Kawamura et al (2010, 2011), Liu et al (2015b), Zhang et al (2018), Saito et al (2020), Zheng et al (2021a) HILI Activates Nrf2/HO-1; increases SIRT1; protects AECIIs by modulating related proteins expression and biological processes Kawamura et al (2013), Sun et al (2017), Lu et al (2018) VILI Reduces inflammatory responses at local and systemic level; increases the early activation of NF-κB Huang et al (2010, 2011) Irradiation-induced lung injury Reduces ROS and apoptosis in A549 cells; reduces lung fibrosis Terasaki et al (2011) Burn induced ALI Attenuates oxidative stress and inflammation; may modulate SIRT1 Fang et al (2011), Bai et al (2015), Qin et al (2017) ALI induced by other causes The protective effects are mainly by inhibiting oxidative stress, inflammation, apoptosis Diao et al (2016), Hong et al (2016), Ying et al (2017),Terasaki et al (2019) …”

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confidence: 99%

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Molecular hydrogen is a potential protective agent in the management of acute lung injury

Zhang

2022

Mol Med

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Acute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill patients. Treatment methods to alleviate the pathogenesis of ALI have improved to a great extent at present. Although the efficacy of these therapies is limited, their relevance has increased remarkably with the ongoing pandemic caused by the novel coronavirus disease 2019 (COVID-19), which causes severe respiratory distress syndrome. Several studies have demonstrated the preventive and therapeutic effects of molecular hydrogen in the various diseases. The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19.

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Section: Sepsis-induced Alimentioning

confidence: 99%

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confidence: 99%

Molecular hydrogen is a potential protective agent in the management of acute lung injury

Zhang

2022

Mol Med

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“…Neutrophils are great producers of ROS and play a role in ageing [ 44 ]. H 2 reduces neutrophil infiltration in the injured tissue [ 45 ], potentially decreasing the generation of ROS. MPO is a heme-containing peroxidase that is mainly expressed in neutrophils.…”

Section: Potential Mechanisms Of Molecular H 2 Act...mentioning

confidence: 99%

Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases

Zhang

2022

Oxidative Medicine and Cellular Longevity

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Ageing is a physiological process of progressive decline in the organism function over time. It affects every organ in the body and is a significant risk for chronic diseases. Molecular hydrogen has therapeutic and preventive effects on various organs. It has antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level. It also activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes. Through its antioxidative effect, hydrogen maintains genomic stability, mitigates cellular senescence, and takes part in histone modification, telomere maintenance, and proteostasis. In addition, hydrogen may prevent inflammation and regulate the nutrient-sensing mTOR system, autophagy, apoptosis, and mitochondria, which are all factors related to ageing. Hydrogen can also be used for prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer. This paper reviews the basic research and recent application of hydrogen in order to support hydrogen use in medicine for ageing prevention and ageing-related disease therapy.

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“…Our previous studies have shown that hydrogen (H 2 ) alleviates lung injury during sepsis by upregulating Trx1 [16]. H 2 has also been reported to inhibit MMP-9 activity in order to reduce brain infarction and improve neurological function [17].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen attenuates postoperative pain through Trx1/ASK1/MMP9 signaling pathway

Ruan

Jia

et al. 2023

J Neuroinflammation

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Background Postoperative pain is a serious clinical problem with a poorly understood mechanism, and lacks effective treatment. Hydrogen (H2) can reduce neuroinflammation; therefore, we hypothesize that H2 may alleviate postoperative pain, and aimed to investigate the underlying mechanism. Methods Mice were used to establish a postoperative pain model using plantar incision surgery. Mechanical allodynia was measured using the von Frey test. Cell signaling was assayed using gelatin zymography, western blotting, immunohistochemistry, and immunofluorescence staining. Animals or BV-2 cells were received with/without ASK1 and Trx1 inhibitors to investigate the effects of H2 on microglia. Results Plantar incision surgery increased MMP-9 activity and ASK1 phosphorylation in the spinal cord of mice. MMP-9 knockout and the ASK1 inhibitor, NQDI-1, attenuated postoperative pain. H2 increased the expression of Trx1 in the spinal cord and in BV-2 cells. H2 treatment mimicked NQDI1 in decreasing the phosphorylation of ASK1, p38 and JNK. It also reduced MMP-9 activity, downregulated pro-IL-1β maturation and IBA-1 expression in the spinal cord of mice, and ameliorated postoperative pain. The protective effects of H2 were abolished by the Trx1 inhibitor, PX12. In vitro, in BV-2 cells, H2 also mimicked NQDI1 in inhibiting the phosphorylation of ASK1, p38, and JNK, and also reduced MMP-9 activity and decreased IBA-1 expression induced by LPS. The Trx1 inhibitor, PX12, abolished the protective effects of H2 in BV-2 cells. Conclusions For the first time, the results of our study confirm that H2 can be used as a therapeutic agent to alleviate postoperative pain through the Trx1/ASK1/MMP9 signaling pathway. MMP-9 and ASK1 may be the target molecules for relieving postoperative pain.

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Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression

Cited by 6 publications

References 43 publications

Molecular hydrogen is a potential protective agent in the management of acute lung injury

Molecular hydrogen is a potential protective agent in the management of acute lung injury

Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases

Hydrogen attenuates postoperative pain through Trx1/ASK1/MMP9 signaling pathway

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