Title:Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO−1 and NF-kB Pathways
Volume: 28
Issue: 30
Author(s): Roberta Fusco, Rosalba Siracusa, Enrico Gugliandolo, Alessio Filippo Peritore, Ramona D’Amico, Marika Cordaro, Rosalia Crupi, Daniela Impellizzeri, Chiara Gomiero, Salvatore Cuzzocrea* Rosanna Di Paola*
Affiliation:
- Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, n 31, Messina 98166,Italy
- Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, n 31, Messina 98166,Italy
Keywords:
Vascular injury, inflammation, oxidative stress, Nrf2, NF-kB, rutin.
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 1:1 (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 β, 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.