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

Abstract

BACKGROUND\nVascular 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.\n\n\nOBJECTIVE\nOur 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 1:1 (PEA/RUT). The anti-inflammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has important pharmacological actions, including antioxidant and vasoprotective.\n\n\nMETHODS\nAs 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.\n\n\nRESULTS\nThis study demonstrated that after fourteen days carotid ligation there is a substantial structural change in the vessel morphology, with inflammatory cells 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\uf020\uf062, IL-6 and TNF-\uf020\uf061), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway).\n\n\nCONCLUSIONS\nOur data clearly demonstrate the beneficial effect of PEA/RUT administration in reducing inflammation, oxidative stress and vascular damage.