Mitigation of acute lung injury by semaglutide: role of inflammatory and oxidative stress pathways

Endotoxic disease Increased production of pro-inflammatory cytokines during bacterial infection is caused by high endotoxin levels, the protective effect of semaglutide on endotoxemia-induced acute lung injury was investigated in this research. twenty-four adult mice of the Swiss-Albano strain, aged 8-14 weeks and weighing between 25- 40 grams, were randomly divided into four groups. The groups were as follows: control (undergoing laparotomy without cecal ligation and puncture), endotoxemia (undergoing cecal ligation and puncture), vehicle (receiving normal saline for 1 week), and treatment (receiving semaglutide at a dose of 0.06mg/kg once daily subcutaneously for 1 week prior to cecal ligation and puncture). The scarification of animals was done 24 hours following the CLP treatment, and their lung tissues were utilized for histological investigation as well as the assessment of inflammatory mediators (IL-6, TNF-α, IL-1B, and NF-KB) and oxidative markers (MDA). The levels of lung tissue, inflammatory mediators, and oxidative stress were considerably elevated (P<0.05) in both the endotoxemia and vehicle groups compared to the control group. The treatment group exhibited significantly reduced levels of inflammatory and oxidative stress mediators compared to the endotoxemia and vehicle groups, with a statistical significance of P<0.05. Microscopically, mice in the endotoxemia and vehicle groups exhibited pronounced lung tissue damage. However, this damage was significantly (P<0.05) mitigated in the group treated with semaglutide. Semaglutide had the capacity to alleviate acute lung damage in male mice exposed to endotoxemia generated by CLP through a decrease in pro-inflammatory cytokines (such as interleukin-1β, interleukin-6, TNF-alpha, and NF-KB) as well as oxidative stress marker (MDA) inside the lung tissue.