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Dabrafenib Alleviates the Effects of Lipopolysaccharides in Endothelial Cells
Saikat Fakir1, Md Matiur Rahman Sarker1, Madan Sigdel1
1College of Pharmacy, University of Louisiana Monroe, School of Basic Pharmaceutical and Toxicological Sciences, Louisiana, USA, Monroe.
Abstract:
The vascular endothelium forms a monolayer which regulates the passage of solutes and gases-including oxygen-between blood and tissues. Endothelial barrier dysfunction has been associated with sepsis, acute lung injury and acute respiratory distress syndrome. Dabrafenib is a food and drug administration-approved v-raf murine sarcoma viral oncogene homolog B1 inhibitor associated with anti-inflammatory responses, which targets the never in mitosis A-related kinase 9 and cyclin-dependent kinase 16. The present study suggests that dabrafenib ameliorates lipopolysaccharide-induced vascular injury by suppressing MLC2, MAPK, and STAT activation; paracellular leak and ROS generation, suggesting its potential use in diseases related to barrier dysfunction.