Hydrogen‐rich and hyperoxygenate saline inhibits lipopolysaccharide‐induced lung injury through mediating NF‐κB/NLRP3 signaling pathway in C57BL/6 mice

Abstract

Background Background: Acute lung injury (ALI) is one kind of frequently occurred emergency in Intensive Care Unite with a high mortality. The underlying causes are uncontrolled inflammatory reactions and intractable hypoxemia, which are difficult to control and improve. In the past 10 years, gas medical studies have found that both hydrogen molecules and oxygen molecules have protective effects on acute lung injury by improving inflammatory reactions and hypoxia, respectively. Oxygen is an oxidant and hydrogen is an antioxidant. In this study, we investigated the combined effect of above two‐gas molecular on lipopolysaccharide (LPS) ‐induced acute lung injury. Methods To clarify whether the combination of hydrogen and oxygen could increase or cancel out the protective effect, an ALI mice model induced by intraperitoneal injection of LPS was established, and the degree of lung tissue and mitochondria damage was evaluated based on the pathological sections, inflammatory factors, wet–dry ratio, bronchoalveolar lavage fluid (BALF). Immunohistochemistry, electron microscopy, western blotting and other detection methods also used to evaluate the therapeutic effect on acute lung injury model. Results We observed that the combined protective effect of hydrogen and oxygen was superior to their respective protective effects, and the specific molecular mechanisms of the two therapies might be different. Conclusion Hydrogen plays a more important role in the inflammatory and anti‐apoptosis mechanisms, while oxygen improves hypoxia of the body, and thus, its molecular mechanism may be closely associated to the hypoxia pathways.

Leucine‐rich repeat kinase 2 is protective during acute kidney injury through its activation of autophagy in podocytes

“…Here we have chosen IR‐induced and LPS‐induced AKI as our research models, since they could well represent two common clinical situations, ischemic organ injury and sepsis. As for the cell signaling pathways underlying AKI, multiple key pathway mediators including Nrf2, MAPK, NLRP3, and NF‐κB have been reported in ischemic injury, nephrotoxic agent‐induced AKI, and LPS‐induced AKI 27,29–31,33–35 . In the current study, however, we revealed the pivotal role of autophagy in IR‐induced and LPS‐induced AKI.…”

“…As for the cell signaling pathways underlying AKI, multiple key pathway mediators including Nrf2, MAPK, NLRP3, and NF-κB have been reported in ischemic injury, nephrotoxic agentinduced AKI, and LPS-induced AKI. 27,[29][30][31][33][34][35] In the current study, however, we revealed the pivotal role of autophagy in IR-induced and LPS-induced AKI.…”

Mitochondria: one of the vital hubs for molecular hydrogen’s biological functions

“…In a few cases, however, the impact of H 2 on mitochondrial indicators seems to exhibit inconsistency among studies. Although H 2 increased ATP production in most cases, Fan et al reported a significant decrease in ATP production in lung tissue of mice with ALI following H 2 treatment (Fan et al, 2022). This may be caused by the LPS-induced increase in neutrophils observed in ALI mice while H 2 reversed the effect of LPS on ATP production.…”

“…In most cases, compared to the disease or stress-induced model group, H 2 treatment exhibited positive effects, including increased mitochondrial ATP production, enhanced mitochondrial respiration, inhibition of mPTP opening, improved MMP, reduced mtROS production, elevated complex I activity, activation of mitophagy, mitochondrial biogenesis, and mitoKATPs, etc. Although H 2 has also been reported to enhance the activity of mitochondrial complex I, III, IV, and V in ovalbumin (OVA) sensitization and challenge-induced allergic airway inflammation mice (Niu et al, 2020) or lipopolysaccharide (LPS)induced acute lung injury (ALI) mice (Fan et al, 2022), the current evidence is still relatively limited, highlighting the need for further research in this area. In a few cases, however, the impact of H 2 on mitochondrial indicators seems to exhibit inconsistency among studies.…”

Downregulation of circ‐ZNF644 alleviates LPS‐induced HK2 cell injury via miR‐335‐5p/HIPK1 axis

“…Lipopolysaccharide (LPS) is an endotoxin that activates the TLR4 pathway to induce a cascade reaction characterized by inflammatory injury in cells 5–7 . LPS is commonly used to induce various cell models, such as lung injury, 8,9 spleen injury, 10 mastitis, 11 and airway inflammation injury 12 . Currently, LPS has been used to induce kidney tubular epithelial cell (HK2) injury to construct AKI cell models in vitro 13,14 …”