Affiliation:
1. Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq.
Abstract
Background and purpose:
Sepsis induces brain dysfunction and there is still a requirement for an unemployed viable restorative approach. This study aimed to investigate the role of dasatinib in the modulation of proinflammatory mediators, attenuating neuroinflammatory response, and it's signaling pathway during endotoxemia.
Experimental approach:
Twenty-four adult male Swiss-albino mice were randomized into four groups: sham (undergo laparotomy without cecal ligation and puncture, sepsis (laparotomy with cecal ligation and puncture), vehicle-dimethyl sulfoxide, dasatinib (20 mg/kg/day) intraperitoneally. Brain tissue used for assessment of interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α), IL-10, Toll-like receptor 4 (TLR4), protein kinase B (AKT), phosphoinositide 3-kinases (PI3K), signal transducer and activator of transcription 3 (STAT3), and histopathological examination.
Findings/Results:
Brain tissue levels of TNF-α, IL-6, and IL1 β were higher in the sepsis group than in the sham and vehicle groups. The dasatinib group had considerably lower tissue levels of these markers and significantly higher tissue values of IL-10 than the sepsis and vehicle groups. The sham group had much lower tissue values of TLR4, AKT, STAT3, and PI3k than in sepsis and vehicle groups. Furthermore, tissue levels of these markers in the dasatinib group were considerably lower than those in the sepsis and vehicle groups. Histopathology demonstrated that dasatinib might considerably reduce brain damage and the intensity of neuroinflammation when compared to sepsis and vehicle groups that showed extensive brain inflammation and damage.
Conclusion and implication:
Dasatinib attenuated endotoxemia-induced acute brain damage in mice via modulating effects on TLR4, PI3K, AKT, and STAT3 downstream signaling pathways.
Reference32 articles.
1. Protective effect of liraglutide from acute renal injury during endotoxemia in mice mode;Hassan;Lat Am J Pharm,2022
2. Nephroprotective effect of celastrol in an experimental model of endotoxemia;Hussein;Bull Nal Insti,2022
3. Protective effect of empagliflozin from acute renal injury during endotoxemia in mice model;Jawad;Lat Am J Pharm,2022
4. Nephroprotective effect of melatonin in sepsis induces renal injury: CLP mice model;Hamza;Lat Am J Pharm,2022
5. Potential protective effect of ibrutinib from acute brain injury during endotoxemia in mice;Mohammad;Lat Am J Pharm,2022