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 via PubMed
Summary
AI-generated from the abstractEsketamine reduced acute lung injury caused by limb ischemia-reperfusion in a rat model. Treatment lowered pulmonary edema, inflammatory cell infiltration, and oxidative stress, as shown by decreased MDA and increased SOD levels. It also reduced inflammatory cytokines in bronchoalveolar fluid and serum. The protective effect involved suppression of the TLR4/NF-κB/NLRP3 pathway; activating that pathway with LPS reversed esketamine's benefits. The findings suggest esketamine may be a potential therapy for acute lung injury.
Study at a glance
| 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. |
| Citations | 1 |
| Key finding | 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.