Sevoflurane reduces lipopolysaccharide-induced apoptosis and pulmonary fibrosis in the RAW264.7 cells and mice models to ameliorate acute lung injury by eliminating oxidative damages

Abstract

Objectives Sevoflurane is identified as an effective candidate drug for acute lung injury (ALI) treatment, but its curing effects and detailed mechanisms have not been fully disclosed. The present study was designed to resolve this academic issue. Methods The ALI mice models were established, and Hematoxylin-eosin staining assay was performed to examine tissue morphologies. Cell viability was determined by CCK-8 assay, and Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The expression levels of proteins were determined by performing Western Blot analysis and immunofluorescence staining assay. ROS levels were examined by using DCFH-DA staining assay. Results In this study, we investigated this issue and the ALI models were respectively established by treating the BALB/c mice and the murine macrophage cell line RAW264.7 with different concentrations of lipopolysaccharide (LPS) in vivo and in vitro, which were subsequently subjected to sevoflurane co-treatment. The results showed that sevoflurane reduced LPS-induced ALI in mice and suppressed LPS-triggered oxidative stress and apoptotic cell death in the RAW264.7 cells. Interestingly, we evidenced that the elimination of reactive oxygen species (ROS) by N-acetyl-L-cysteine (NAC) reversed LPS-induced cell apoptosis in RAW264.7 cells. Then, we verified that sevoflurane suppressed oxidative damages to restrain LPS-induced apoptotic cell death in the RAW264.7 cells through activating the anti-oxidant Keap1/Nrf2 pathway. Mechanistically, sevoflurane down-regulated Keap1 and upregulated Nrf2 in nucleus to activate the downstream anti-oxidant signaling cascades, which further ameliorated LPS-induced cell apoptosis and lung injury by eliminating oxidative damages. Discussion Taken together, our study illustrated that the sevoflurane attenuates LPS-induced ALI by inhibiting oxidative stress-mediated apoptotic cell death and inflammation, and the Keap1/Nrf2 pathway played an important role in this process.

Neutrophilic Inflammation and Reactive Oxygen Species Production Promotes Necrotizing Enterocolitis induced Lung Injury in Mice

“…As previously reported, the classical Keap1-Nrf2 pathway is pivotal for regulating oxidative stress, and in oxidative stress conditions, the activated Nrf2 transfers from the cytoplasm to the nucleus to activate the downstream anti-oxidant effectors through binding to ARE [14]. Through LPS promotion and NAC suppression, we found that the related genes on the pathway of Keap1-Nrf2 had changed accordingly.…”

“…Many studies have suggested that regulation of Keap1-Nrf2 signaling pathways can affect the development of lung injury [14]. Speci cally, Huang et al [15] suggest that this pathway regulates endoplasmic reticulum stress, apoptosis, and autophagy to attenuate LPS-induced ALI.…”

Sevoflurane blocks KLF5‐mediated transcriptional activation of ITGB2 to inhibit macrophage infiltration in hepatic ischemia/reperfusion injury

“…Data shown are the mean ± SD (n = 3 per group). Data were compared by unpaired ttest or two-way ANOVA using a significance level of p < 0.05. ischemia, 27,28 we found that it was KLF5 that linked the regulatory effects of Sevo on macrophage infiltration to ITGB2 expression. In conclusion, Sevo attenuated I/R-associated liver damage in mice by exerting its anti-apoptotic and anti-inflammatory effects.…”

Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

“…Propidium Iodide (PI) is a nucleic acid dye that causes the cell nucleus to become red by damaging cell membranes. Thus, Annexin V with PI can be used to distinguish cells at different stages of apoptosis [ 55 ]. MRC-5 cells at logarithmic growth phase were seeded in 6-well plates (1 × 10 5 ).…”