Focal Adhesion Kinase Inhibitor Inhibits the Oxidative Damage Induced by Central Venous Catheter via Abolishing Focal Adhesion Kinase-Protein Kinase B Pathway Activation

Abstract

The vascular injury induced by central venous catheter (CVC) indwelling is the basis for the occurrence and development of CVC-related complications, such as phlebitis, venous thrombosis, and catheter-related infections. Focal adhesion kinase (FAK) and FAK-protein kinase B (AKT) signaling pathway are of great significance in tissue repair after trauma. Here, we investigated the role and mechanism of the FAK inhibitor (1,2,4,5-phenyltetramine tetrahydrochloride (Y15)) in oxidative damage caused by CVC. EA.hy926 cells were divided into the control group (normal control), CVCs+scratches group (the intercepted CVC segments coculturing with scratched EA.hy926 cells), and CVCs+scratches+Y15 group (Y15 was added to the cell culture supernatant with CVCs + scratches at a final concentration of 50 μmol·L-1). New Zealand rabbits were randomly divided into the control group (normal control), CVC group (CVC was inserted through the rabbit’s right jugular vein to the junction of the right atrium and superior vena cava), and CVC+Y15 group (CVC was immersed in a 50 μmol·L-1 Y15 solutions before insertion). The levels of markers and proteins related to oxidative damage in cells, cell culture supernatant, serum, and external jugular vein were measured by commercial kits and western blot, respectively. We found that Y15 treatment significantly decreased ROS and MDA levels and increased cell viability, NO, and SOD levels in a time-dependent manner in rabbit serum and cell culture supernatant. In addition, Y15 effectively reduced the CVC-induced pathological changes of damaged vascular tissues. Y15 also downregulated the levels of p-FAK Tyr 397 and p-Akt Ser 473 in damaged external jugular vein and EA.hy926 cells. These findings suggest that Y15 alleviated CVC-induced oxidative damage to blood vessels by suppressing focal FAK-Akt pathway activation.

Progress in Research on the Mechanisms and Interventions of Phlebitis from the Perspective of Vascular Endothelial Cell and Signaling Pathway

“…It indicated that Y15 could not only reduce CVC-induced oxidative stress injury to blood vessels but also prevent phlebitis and thrombosis caused by CVC through inhibiting the activation of FAK-AKT pathway. 8 …”

“…It indicated that Y15 could not only reduce CVC-induced oxidative stress injury to blood vessels but also prevent phlebitis and thrombosis caused by CVC through inhibiting the activation of FAK-AKT pathway. 8 Wang et al also confirmed that Y15 had anti-inflammatory effects against vascular endothelial injury triggered by CVC combined with 5-FU by regulating the FAK-NF-κB signaling pathway. 9 EA.hy926 cells were randomly assigned to three groups: normal control, model group [ie, a cell inflammatory injury model induced by three scratches (2 cm each), three CVC (1 cm) segments, and 1 g/L 5-FU 80 μL], and experimental group (ie, 50 μL of 2 mmol/L Y15 was added to the model group).…”

Effect of a parenteral fish‐oil‐containing lipid emulsion on liver lipid perioxidation and antioxidative defenses in Lewis rats

“…Our surgical stress model comprised the jugular central venous catheterization (CVC) and was performed according to a standardized technique 11 . CVC has previously been shown to induce oxidative stress in animal models 12 . Within the experimental groups, this procedure also enabled the parenteral infusion of LE by using a specific catheter that allowed a connection to a gyratory swivel apparatus, which ensured partial free mobility for the animals 13 …”

An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS‐CoV‐2 infection: A hypothesis

“…Protein kinase B (Akt) is a potential pharmacological target for the advanced‐stage SARS‐CoV‐2 infection; its inhibition will effectively suppress the pathological fibroproliferation, cytokine storm, platelet activation, and inflammation associated with COVID‐19 (Basile et al, 2021 ). Furthermore, this inhibition could prevent scarring and lung injuries (Wang, Lin, et al, 2021 ). In addition, since inhibition of Akt by pharmacologic inhibitors has also been reported to reduce ACE2 expression, a crucial receptor for the viral entry into the respiratory system cells, targeting Akt for COVID‐19 seems to be a feasible option (Somanath, 2020 ).…”