title: Effects of palmitoylethanolamide and silymarin combination treatment in an animal model of kidney ischemia and reperfusion.
abstract: The aim of this study was to investigate the efficacy of PEA+silymarin as a combination treatment in a mouse model of renal I/R and to verify whether PEA+silymarin could exert more potent effects compared to the single substances even if administered at lower doses. Mice were subjected to bilateral renal artery occlusion (30min) and reperfusion (6h) and received intraperitoneally silymarin (100, 30 and 10mg/kg) or PEA (1mg/kg) or PEA (1mg/kg)+silymarin (10mg/kg) 15min before release of clamps. Specific indicators of renal dysfunction, tubular injury, myeloperoxidase activity and malondialdehyde levels were measured. The nuclear factor κB pathway and apoptotic mechanisms were also investigated. The treatment with silymarin reduced kidney dysfunction, histological damage, neutrophil infiltration and oxidative stress in a dose dependent manner. Furthermore, PEA+silymarin showed a significant potentiated effect. Therefore, NF-κB and apoptosis pathways were also significantly inhibited. Our results clearly demonstrate that PEA+silymarin treatment attenuated the degree of renal inflammation.
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy. Electronic address: dimpellizzeri@unime.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy. Electronic address: bruschettag@unime.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruschetta
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: aahmad@unime.it.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy. Electronic address: rcrupi@unime.it.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy. Electronic address: rosiracusa@gmail.com.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Siracusa
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy. Electronic address: dipaolar@unime.it.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy. Electronic address: ipaterniti@unime.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: Prismic Pharmaceuticals, Inc., Hayden Corporate Center, Suite 100 8283 North Hayden Road, Scottsdale 85258, Arizona. Electronic address: prosdocimimarco@gmail.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Prosdocimi
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy. Electronic address: eesposito@unime.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Biological and Environmental Sciences, Uni versity of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy; Manchester Biomedical Research Centre, Manchester Royal Infirmary, School of Medicine, University of Manchester, UK. Electronic address: salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000577:Amides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D053818:Chymases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010169:Palmitic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000577:Amides; D016207:Cytokines; D004983:Ethanolamines; D009566:Nitrates; D009573:Nitrites; D010169:Palmitic Acids; D012838:Silymarin; D051996:Transcription Factor RelA; C002744:3-nitrotyrosine; D014443:Tyrosine; C005958:palmidrol; D053818:Chymases
keywords: Apoptosis; Cytokines; Inflammation; Oxidative stress; Renal disease