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Volume 15, Issue 2 (2023)
Iran J War Public Health 2023, 15(2): 199-205 |
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Received: 2023/04/9 | Accepted: 2023/05/27 | Published: 2023/07/18
Received: 2023/04/9 | Accepted: 2023/05/27 | Published: 2023/07/18
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Shnaien A, Mohammad A, Hassan E. Neuroprotective Effects of Semaglutide in Endotoxemia Mouse Model. Iran J War Public Health 2023; 15 (2) :199-205
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1- Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq
Abstract (880 Views)
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.
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.
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