ticagrelor and Endotoxemia

The use of acetylsalicylic acid (ASA) is associated with improved outcome in patients with sepsis, and P2Y

Topics: Adenosine; Administration, Intravenous; Adolescent; Adult; Aspirin; Cells, Cultured; Clopidogrel; Cytokines; Drug Therapy, Combination; Endotoxemia; Endotoxins; Healthy Volunteers; Humans; Inflammation; Inflammation Mediators; Male; Netherlands; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome; Young Adult

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. This study aimed to investigate the potential protective effect of the lungs in sepsis by modulating inflammatory and oxidative stress markers. Twenty-four adult male Swiss-albino mice, aged 8-12 weeks and weighing 20-30 g, were divided into four equal groups (n=6): sham (laparotomy only), CLP (laparotomy plus cecal ligation and puncture), vehicle (DMSO administered one hour before CLP), and Ticagrelor (50 mg/kg IP administered one hour before CLP). Tissue levels of pro-inflammatory and oxidative stress markers in the lung were assessed using ELISA. F2 isoprostane levels were significantly higher in the sepsis group (p<0.05) compared to the sham group, while Ticagrelor significantly decreased the inflammatory and oxidative stress markers compared to the sepsis group. All mice in the sepsis group had considerable (p=0.05) lung tissue damage, but Ticagrelor considerably decreased lung tissue injury (p=0.05). Furthermore, Ticagrelor was found to reduce tissue cytokine levels of the lung (IL-1, TNF a, IL-6, F2 isoprostane, GPR 17, MIF) in male mice during CLP-induced polymicrobial sepsis by modulation of pro-inflammatory and oxidative stress cascade signaling pathways.

Topics: Animals; Endotoxemia; F2-Isoprostanes; Lung; Male; Mice; Sepsis; Ticagrelor