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2000
Volume 26, Issue 1
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873
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Abstract

Background

Esketamine has shown promise in mitigating tissue damage caused by ischemia-reperfusion injury, making it a potential therapeutic candidate for acute lung injury (ALI) induced by limb ischemia-reperfusion (LIR-ALI).

Objective

This study sought to explore the role and mechanism of esketamine in the LIR-ALI rat model.

Methods

The effects of esketamine on the LIR-ALI rats model were evaluated through histopathological examination, assessment of pulmonary edema, measurement of MDA and SOD levels, and analysis of inflammatory cytokine levels (IL-1β, .) in the bronchoalveolar fluid (BALF) and serum. Western blot analysis was used to assess the expressions of TLR4, NF-κB, and NLRP3. TLR4 agonist, LPS, was used to validate the role of NF-κB/NLRP3 pathway in LIR-ALI.

Results

Esketamine significantly alleviated LIR-induced ALI by reducing pulmonary edema, inflammatory cell infiltration, and oxidative stress. Elevated MDA content and suppressed SOD activity were significantly reversed by esketamine, along with inactivity of the TLR4/NF-κB/NLRP3 pathway. Esketamine treatment reduced inflammatory response in BALF and serum. TLR4 activation by LPS reversed the ameliorative effects of esketamine on LIR-ALI.

Conclusion

Esketamine protected against LIR-induced ALI by mitigating oxidative stress and suppressing the TLR4/NF-κB/NLRP3 axis. These findings highlight the potential therapeutic value of esketamine for ALI.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-04-29
2025-12-15

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Esketamine Reduces Lung Injury Caused by Limb Ischemia-Reperfusion by Regulating Oxidative Stress <span class="jp-italic">via&nbsp;</span> the TLR4/NF-κB/NLRP3 Pathway
Endocr Metab Immune Disord Drug Targets 26, E18715303393744 (2026); https://doi.org/10.2174/0118715303393744250423100211
/content/journals/emiddt/10.2174/0118715303393744250423100211
/content/journals/emiddt/10.2174/0118715303393744250423100211
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  • Article Type:     Research Article
Keyword(s): acute lung injury; Esketamine; inflammatory cytokine; limb ischemia-reperfusion; oxidative stress; TLR4/NF-κB/NLRP3 pathway

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