Comicronized PEA and Rutin reduces inflammation and oxidative stress in a mouse model of vascular injury

Acute and chronic inflammation responses are important risk factors for vascular remodeling processes such as in atherosclerosis, arteriosclerosis and restenosis. Inflammation and oxidative stress in the intimal region after a vascular damage are key events in the development of neo intimal hyperplasia. Sustained failure to counteract the excessive production of reactive oxygen species (ROS) and dysregulation of the antioxidant defence system in the endothelium elicits cellular damage and dysfunction. Palmitoylethanolamide (PEA) an endogenous fatty acid amide belonging to the N‐acylethanolamine family, has anti‐inflammatory and neuroprotective effects. However, PEA lacks direct capacity to prevent formation of free radicals. Rutin is a kind of flavonoid glycoside known as Vitamin P and has antiplatelet, antiviral and antihypertensive properties, as well as strengthing the capillaries of blood vessels, which are the results of its high radical scavenging activity and antioxidant capacity. Thus, the combination of PEA with rutin could have beneficial effects on inflammatory process and oxidative stress. The aim of this study was to investigate the protective effects of a new comicronized compound Palmitoylethanolamide with antioxidant Rutin (Rutamid) in a ratio 1:1 at dose of 10mg/kg (daily oral adminstration) in an experimental model of vascular damage, which involves the complete ligature of the left carotid artery for 14 days. This model showed that 14 days after carotid artery ligation there was a significant structural change within the vessel, and an important involvement of inflammatory pathways in the progression of this disease. Rutamid treatment reduces vessel damage, adhesion molecules expression such as intercellular adhesion molecules‐1(ICAM‐1) and vascular cell adhesion molecules‐1(V‐CAM), proinflammatory cytokines production (Tumor Necrosis Factor alpha (TNF‐) and Interleukin 1 beta(IL‐1), the inducible nitricoxide synthase(iNOS) and Poly(ADP‐ribose) polymerase (PAR), formation. Nuclear factor kappa‐B and NRF‐2 pathways activation and apoptosis were evaluated. Our results clearly demonstrated that treatment with Rutamid was able to reduce vascular damage and attenuates the inflammatory process and oxidative stress. Rutamid could represent a new therapeutic strategy in the treatment of conditions associated to vascular damage.