. 2021 Sep 28;56(12):2889–2896. doi: 10.1038/s41409-021-01383-x

Table 1.

Proposed cellular effects of defibrotide.

Cellular effects	Preclinical and clinical evidence
Anti-inflammatory effects	• Reduces release of inflammatory mediators (IL-6, thromboxane A2, LTB4, TNF) [3]
Antioxidant effects	• Attenuates ROS generation and restore endothelial NOS levels during oxidative stress [26]
Protective effects	• Downregulates HDACs [29] • Inhibits the expression of ROS, ICAM-1, vWF, TLR4, VCAM-1, and TF to levels consistent with normal endothelial function [29] • Inhibits the activation of PI3K/AKT and p38 MAPK, as well as a major effector p70S6K, in endothelial cells [26, 33, 36]

Cellular effects

Preclinical and clinical evidence

Anti-inflammatory effects

• Reduces release of inflammatory mediators (IL-6, thromboxane A2, LTB4, TNF) [3]

Antioxidant effects

• Attenuates ROS generation and restore endothelial NOS levels during oxidative stress [26]

Protective effects

• Downregulates HDACs [29]

• Inhibits the expression of ROS, ICAM-1, vWF, TLR4, VCAM-1, and TF to levels consistent with normal endothelial function [29]

• Inhibits the activation of PI3K/AKT and p38 MAPK, as well as a major effector p70S6K, in endothelial cells [26, 33, 36]

IL interleukin, LTB4 leukotriene B4, TNF tumor necrosis factor, ROS reactive oxygen species, NOS nitric oxide synthase, HDAC histone deacetylases, ICAM intercellular adhesion molecule, vWF von Willebrand factor, TLR toll-like receptor, VCAM vascular cell adhesion molecule, TF tissue factor, PI3K/AKT phosphatidylinositol 3-kinase/Akt, MAPK mitogen-activated protein kinase.