Esketamine Reduces Lung Injury Caused by Limb Ischemia-Reperfusion by Regulating Oxidative Stress via the TLR4/NF-κB/NLRP3 Pathway.
Endocrine, metabolic & immune disorders drug targets – April 29, 2025
Source: PubMed
Summary
A breakthrough in treating lung damage reveals that esketamine, a promising medication, can protect against acute lung injury caused by restricted blood flow to limbs. The drug works by controlling harmful oxidative stress and reducing inflammatory responses in lung tissue. It achieves this by regulating a key cellular pathway that affects inflammation, leading to better lung function and reduced tissue damage.
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.