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Volume 15, Issue 1 (2023)
Iran J War Public Health 2023, 15(1): 35-42 |
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Received: 2022/12/27 | Accepted: 2023/02/20 | Published: 2023/03/11
Received: 2022/12/27 | Accepted: 2023/02/20 | Published: 2023/03/11
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Abd Uljaleel A, Hassan E, Mohammad A, Hadi N. Protective Effect of Dulaglutide on Lung Injury in Endotoxemia Mouse Model. Iran J War Public Health 2023; 15 (1) :35-42
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1- Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq
Abstract (769 Views)
Aims: Endotoxemia is the most common condition in patients treated in critical care units. This study aimed to investigate if dulaglutide may help to protect the lungs during endotoxemia by modulating the inflammatory and oxidative stress pathways. This study is self-funded. All authors contributed to the costs.
Materials & Methods: 20 adult male Swiss-albino mice aged 9–12 weeks, weighted 25–35g, were randomized into four equal groups (n=5), sham group (laparotomy without Cecal Ligation and Puncture (CLP), CLP group (laparotomy with CLP), vehicle group (normal saline 2 weeks before CLP), and dulaglutide group (0.6mg/kg twice weekly S.C for 2 weeks before CLP). After 24 hrs of sepsis, lung tissue was harvested and used to assess IL-6, Interleukin-IL-1β, TNF-α, MIF, TLR4, and 8-isoPGF2α, as well as histological examination.
Findings: Lung tissue levels of IL-6, IL-1β, TNF-α, MIF, TLR4, and F2-isoprostane were significantly higher in the sepsis group compared to the sham group (p<0.05), while dulaglutide group showed significantly lower level in these inflammatory mediators and oxidative stress compared to sepsis group (p<0.05). Histologically, all mice in the sepsis group showed a significant lung tissue injury (p<0.05), but this injury was significantly reduced in the dulaglutide pre-treated group (p<0.05).
Conclusion: Dulaglutide can attenuate acute lung injury during CLP-induced endotoxemia in mice through its modulating effects on TLR4 and oxidative stress, downstream signaling pathways, and subsequently decreased lung tissue levels of pro-inflammatory mediators.
Materials & Methods: 20 adult male Swiss-albino mice aged 9–12 weeks, weighted 25–35g, were randomized into four equal groups (n=5), sham group (laparotomy without Cecal Ligation and Puncture (CLP), CLP group (laparotomy with CLP), vehicle group (normal saline 2 weeks before CLP), and dulaglutide group (0.6mg/kg twice weekly S.C for 2 weeks before CLP). After 24 hrs of sepsis, lung tissue was harvested and used to assess IL-6, Interleukin-IL-1β, TNF-α, MIF, TLR4, and 8-isoPGF2α, as well as histological examination.
Findings: Lung tissue levels of IL-6, IL-1β, TNF-α, MIF, TLR4, and F2-isoprostane were significantly higher in the sepsis group compared to the sham group (p<0.05), while dulaglutide group showed significantly lower level in these inflammatory mediators and oxidative stress compared to sepsis group (p<0.05). Histologically, all mice in the sepsis group showed a significant lung tissue injury (p<0.05), but this injury was significantly reduced in the dulaglutide pre-treated group (p<0.05).
Conclusion: Dulaglutide can attenuate acute lung injury during CLP-induced endotoxemia in mice through its modulating effects on TLR4 and oxidative stress, downstream signaling pathways, and subsequently decreased lung tissue levels of pro-inflammatory mediators.
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