Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury Through Modulation Of The Nrf2/Ho-1 And Nf-Kb Pathways

Background: Vascular remodeling processes induced by acute and chronic in-juries are characterized by inflammation and oxidative stress. In arteriosclerosis, atheros-clerosis, and restenosis, the progression of neointimal hyperplasia is a key event of vascu-lar damage. Objective: Our study was aimed to investigate the inflammation and oxidative stress de-velopment during vascular impairment and the potential efficacy of treatment of new mi-cro composite N-palmitoylethanolamine/Rutin at a ratio of 1:1 (PEA/RUT). The anti-in-flammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has impor-tant 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 infiltra-tion 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), proin-flammatory cytokines production (IL-1 beta, IL-6 and TNF-alpha), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway). Conclusion: Our data clearly demonstrate the beneficial effect of PEA/RUT administra-tion in reducing inflammation, oxidative stress, and vascular damage.