Esketamine Reduces Lung Injury Caused by Limb Ischemia-Reperfusion by Regulating Oxidative Stress via the TLR4/NF-κB/NLRP3 Pathway.
Meng Wang, Qian Ma, Wenjuan Wang, Jiawei Cun, Heng Wen
Endocrine, metabolic & immune disorders drug targets April 29, 2025 DOI: 10.2174/0118715303393744250423100211 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats with limb ischemia-reperfusion-induced acute lung injury |
| Intervention | Esketamine |
| Topics | Esketamine |
| Keywords | Tlr4/nf-κb/nlrp3 pathway Acute lung injury Inflammatory cytokine Limb ischemia-reperfusion Oxidative stress. Lung-injury-treatment Esketamine-therapy Inflammation-research Oxidative-stress Medical-breakthrough |
| Citations | 1 |
| Key points | Esketamine protected against limb ischemia-reperfusion-induced acute lung injury by reducing oxidative stress and suppressing the TLR4/NF-κB/NLRP3 pathway. |
Abstract
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). This study sought to explore the role and mechanism of esketamine in the LIR-ALI rat model. 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, etc.) 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 LIRALI. 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. 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.