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Global Translational Medicine Hydrogen for acute lung injury

cytoplasmic protein chaperone Keap1, which inhibits Nrf2 Province Natural Science Foundation of Shandong (No.
activity. However, under the influence of oxidative stress, Nrf2 ZR2020KH008 and No. ZR2012HL18), the Province
and Keap1 proteins dissociate and translocate into the nucleus. Science and Technology Development Foundation of
There, they bind to the GCTGAGTCA site of antioxidant Shandong (2014GSF118105), the Introduction Plan of
response element (ARE) sequence proteins, inducing the Young Creative Talents in Colleges and Universities of
expression of antioxidant proteins (SOD, CAT, etc.) and phase Shandong Province (No. 205), and Shandong Province
II detoxification enzymes, such as heme-oxygenase-1 (HO-1) Technology Contract (2022370702103646).
to make the effect of anti-oxidative stress [59,60] .
Conflict of interest
4.5. Limitations
The authors declare that there is no conflict of interest
This meta-analysis has several limitations. First, the number of regarding the publication of this article.
studies available for inclusion in this meta-analysis is limited,
although this meta-analysis is, to the best of our knowledge, Author contributions
the first to discuss how different administration methods of Conceptualization: Guoshen Zhong, Nana Yang, Na Tian
hydrogen affect the treatment effects of ALI animal models. Formal analysis: Guoshen Zhong, Lingyu Kong, Mei Yang
Second, there is significant heterogeneity among the included Investigation: Mei Yang
studies, and the average quality scores of the studies are Methodology: Kaixuan Lv, Lichun Zhang
relatively low, indicating a potential publication bias. Third, Writing – original draft: Guoshen Zhong
there is a lack of research on the direct comparison between Writing – review & editing: Nana Yang, Yanhua Shi
the effects of inhaling H and injecting hydrogen saline. This
2
limitation makes it difficult to further explore the effects Ethics approval and consent to participate
and the relationship between treatment times for H and Not applicable.
2
hydrogen saline. Finally, the grade evidence indicates that
the results of some included indicators may not be reliable, Consent for publication
suggesting that there are certain issues with the experimental
designs of the ALI animal models. Although the trim and fill Not applicable.
funnel plot and sensitivity analysis provide some reassurance Availability of data
regarding the reliability of the meta-analysis results, it also
underscores the needs for improving the design of animal All data used in the present paper can be obtained from the
experiments in future studies. corresponding authors.
5. Conclusion References

This meta-analysis provides evidence that the therapeutic 1. Butt Y, Kurdowska A, Allen TC, 2016, Acute lung injury:
potential of hydrogen in ALI is mediated through the A clinical and molecular review. Arch Pathol Lab Med,
inhibition of the relevant molecules and proteins related 140: 345–350.
to the NF-κB and p38MAPK signaling pathways, which https://doi.org/10.5858/arpa.2015-0519-RA
reduces inflammation. In addition, hydrogen plays a 2. Matthay MA, Zemans RL, Zimmerman GA, et al., 2019,
role in antioxidant stress by stimulating the expression Acute respiratory distress syndrome. Nat Rev Dis Primers,
of antioxidant proteins through the Nrf2/ARE signaling 5: 18.
pathway. Furthermore, hydrogen can regulate neutrophil https://doi.org/10.1038/s41572-019-0069-0
adhesion and macrophage polarization, suggesting its
potential to inhibit idiopathic pulmonary fibrosis. 3. Cardinal-Fernández P, Lorente JA, Ballén-Barragán A,
et al., 2017, Acute respiratory distress syndrome and diffuse
Acknowledgments alveolar damage. New insights on a complex relationship.
Ann Am Thorac Soc, 14: 844–850.
The authors would like to acknowledge the support https://doi.org/10.1513/AnnalsATS.201609-728PS
provided by the Experimental Animal Center of Weifang
Medical University. 4. Matthay MA, Ware LB, Zimmerman GA, 2012, The acute
respiratory distress syndrome. J Clin Invest, 122: 2731–2740.
Funding https://doi.org/10.1172/JCI60331

This research was supported by the National Natural 5. Williams AE, José RJ, Mercer PF, et al., 2017, Evidence for
Science Foundation of China (No. 81600360), the chemokine synergy during neutrophil migration in ARDS.

Volume 2 Issue 3 (2023) 12 https://doi.org/10.36922/gtm.0379