Neuroprotective Effects of Semaglutide in Endotoxemia Mouse Model

Aims: The present study aimed to examine the neuroprotective effects of semaglutide during endotoxemia and its role in modulating pro-inflammatory mediators. Materials Methods: Twenty-four adult male Swiss albino mice, 8-12 weeks old, weighing 25-35g, were randomly divided into four equal groups (n=6), including sham (laparotomy without cecal ligation and puncture, sepsis (laparotomy with CLP), vehicle (equivalent volume of distilled water before CLP), and semaglutide (40µg/kg/day before CLP). The brain was used for tissue evaluation of TNF-α, IL-6, IL-1β, TLR4, and P-STAT3, as well as for histological examination. Findings: The tissue levels of TNF-α, IL-6 and IL-1β in the sham group were significantly lower than the sepsis and vehicle groups (p 0.05). In the semaglutide group, tissue levels of TNF-α, IL-6, and IL-1β were significantly lower than the sepsis and vehicle groups (p 0.05). The tissue levels of TLR4 and STAT3 in the sham group were significantly lower than the sepsis and vehicle groups (p 0.05). Also, tissue levels of TLR4 and STAT3 in the semaglutide group were significantly lower than the sepsis and vehicle groups (p 0.05). Histopathologically, semaglutide considerably reduced brain damage compared to the sepsis and vehicle groups. Conclusion: Semaglutide can reduce brain dysfunction during CLP-induced polymicrobial sepsis in male mice through its modulating effects on TLR4STAT3 downstream signaling pathways and subsequently reducing inflammatory cytokines TNF-α, IL-6, and IL-1β.