The therapeutic targets and signaling mechanisms of ondansetron in the treatment of critical illness in the ICU.

Background: There is accumulating evidence regarding the benefits of the 5-HT Methods: A bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets and the signaling pathways of ondansetron action against the most common critical illnesses such as acute kidney injury (AKI), sepsis, and acute respiratory distress syndrome (ARDS). Experiments of LPS-stimulated rat neutrophils with ondansetron treatment were conducted to further validate the relevant hypothesis. Results: A total of 198, 111, and 26 primary causal targets were identified from the data for the action of ondansetron against AKI, sepsis, and ARDS respectively. We found that the pathway of neutrophil extracellular traps (NETs) formation is statistically significantly involved in the action of ondansetron against these three critical illnesses. In the pathway of NETs formation, the common drug-disease intersection targets in these three critical illnesses were toll-like receptor 8 ( Conclusion: The excessive formation of NETs may have important research value in the development and progression of critical illness. Ondansetron may reduce excessive inflammatory injury in critical diseases by reducing the formation of NETs via influencing the five targets: