Investigating the impact of selegiline on the NF-kB/NLRP3/Caspase-1 signaling pathway in A549 lung epithelial cells exposed to lipopolysaccharide.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are respiratory conditions associated with high mortality rates, primarily due to intense pulmonary inflammation. Lipopolysaccharide (LPS), an essential constituent of the wall of gram-negative bacteria, has the potential to trigger inflammation, ultimately leading to ALI. This study assessed the protective role of selegiline in mitigating LPS-induced inflammation in A549 cells. A549 cells were divided into seven groups: the negative control (PBS, 100 μM), the positive control (H₂O₂, 100 μM), the LPS group (1 µg/ml), groups treated with selegiline (Sel) (20, 30, and 40 μM) + LPS, and a group receiving Sel (40 μM). Parameters, including cell viability, iNOS activity, levels of SOD, CAT, and GPx, along with the pro-inflammatory cytokines IL-1β and TNF-α, as well as the protein expressions of NF-kB, NLRP3, and Caspase-1, were analyzed. Findings revealed that exposure to LPS increased oxidation and inflammation in A549 cells. Conversely, Sel markedly enhanced antioxidant capacity and diminished the iNOS activity, IL-1β, and TNF-α levels, as well as reduced the expression of inflammatory markers, including NF-kB, NLRP3, and Caspase-1 proteins. These results indicate that Sel may ameliorate LPS-induced pulmonary inflammation through its beneficial properties, including antioxidant and anti-inflammatory effects.