Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO-1 and NF-kB Pathways.

ABSTRACT

BACKGROUND: Vascular remodeling processes induced by acute and chronic injuries are characterized by inflammation and oxidative stress. In arteriosclerosis, atherosclerosis, and restenosis, the progression of neointimal hyperplasia is a key event of vascular damage. OBJECTIVE: Our study was aimed to investigate the inflammation and oxidative stress development during vascular impairment and the potential efficacy of treatment of new micro composite N-palmitoylethanolamine/Rutin at a ratio of 11 (PEA/RUT). The anti-inflammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has important pharmacological actions, including antioxidant and vasoprotective. METHODS: As a model of vascular injury, we used the complete ligature of the left carotid artery for fourteen days and administered PEA/RUT at the dose of 10 mg/Kg. RESULTS: This study demonstrated that after fourteen days of carotid ligation, there is a substantial structural change in the vessel morphology, with inflammatory cell infiltration and reactive oxygen species production. PEA/RUT administration reduced change in vascular morphology, cytokines like monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules expression like intercellular adhesion molecules-1 (ICAM-1), proinflammatory cytokines production (IL-1 ß, IL-6 and TNF- α), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway). CONCLUSION: Our data clearly demonstrate the beneficial effect of PEA/RUT administration in reducing inflammation, oxidative stress, and vascular damage.