title: Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats.
abstract: Obesity-associated nephropathy is considered to be a leading cause of end-stage renal disease. Resveratrol supplementation represents a promising therapy to attenuate kidney injury, but the poor solubility and limited bioavailability of this polyphenol limits its use in dietary intervention. Piceatannol, a resveratrol analogue, has been suggested as a better option. In this study, we aimed to provide evidence of a preventive action of piceatannol in very early stages of obesity-associated nephropathy. Thirty obese Zucker rats were divided into three experimental groups: one control and two groups orally treated for 6 weeks with 15 and 45 mg piceatannol/kg body weight/day. Enzyme-linked immunosorbent assays (ELISA) were used to determine renal and urinary kidney injury molecule-1 (Kim-1), renal fibrosis markers (transforming growth factor β1 and fibronectin) and renal sirtuin-1 protein. Oxidative stress was assessed in the kidney by measuring lipid peroxidation and nitrosative stress (thiobarbituric acid reactive substrates and 3-nitrotyrosine levels, respectively) together with the activity of the antioxidant enzyme superoxide dismutase. Renal fatty acids profile analysis was performed by thin-layer and gas chromatography. Piceatannol-treated rats displayed lower levels of urinary and renal Kim-1. Renal fibrosis biomarkers and lipid peroxidation exhibited a tendency to decrease in the piceatannol-treated groups. Piceatannol treatment did not modify superoxide dismutase activity or sirtuin-1 protein levels, while it seemed to increase the levels of polyunsaturated and omega-6 polyunsaturated fatty acids in the kidneys. Our findings suggest a mild renoprotective effect of piceatannol in obese Zucker rats and the need of intervention at early stages of renal damage.
authors.affiliation: Unit of Metabolism, Cruces University Hospital - BioCruces Health Research Institute, GCV-CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Plaza de Cruces s/n, 48903, Barakaldo, Bizkaia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Llarena
authors.affiliation: Unit of Metabolism, Cruces University Hospital - BioCruces Health Research Institute, GCV-CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Plaza de Cruces s/n, 48903, Barakaldo, Bizkaia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Andrade
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale (INSERM U1048), Toulouse, France.
authors.forename: Mounia
authors.initials: M
authors.lastname: Hasnaoui
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of Basque Country (UPV/EHU), Centro de Investigación Lucio Lascaray, Centro de Investigación Biomédica en Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 01006, Vitoria, Spain.
authors.forename: María P
authors.initials: MP
authors.lastname: Portillo
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Hospital Universitario Miguel Servet, CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Zaragoza, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Arbones-Mainar
authors.affiliation: Department of Gastroenterology, University of the Basque Country (UPV/EHU), Donostia Hospital and Biodonostia Institute and Centro de Investigación Biomédica en Enfermedades Hepáticas (CIBERehd), Instituto de Salud Carlos III, 20014, San Sebastián, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hijona
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Villanueva-Millán
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of Basque Country (UPV/EHU), Centro de Investigación Lucio Lascaray, Centro de Investigación Biomédica en Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 01006, Vitoria, Spain.
authors.forename: Leixuri
authors.initials: L
authors.lastname: Aguirre
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale (INSERM U1048), Toulouse, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Carpéné
authors.affiliation: Unit of Metabolism, Cruces University Hospital - BioCruces Health Research Institute, GCV-CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Plaza de Cruces s/n, 48903, Barakaldo, Bizkaia, Spain. luisjose.aldamiz-echevarazuara@osakidetza.eus.
authors.forename: Luis
authors.initials: L
authors.lastname: Aldámiz-Echevarría
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000652:urine; D019587:Dietary Supplements; D005355:Fibrosis; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008297:Male; D009765:Obesity / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009929:Organ Size; D018384:Oxidative Stress; D011897:Random Allocation; D011924:Rats, Zucker; D051437:Renal Insufficiency / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D013267:Stilbenes; D017392:Thiobarbituric Acid Reactive Substances; D014443:Tyrosine; C110936:Havcr1 protein, rat; C002744:3-nitrotyrosine; C041525:3,3',4,5'-tetrahydroxystilbene
keywords: Nephropathy; Obesity complications; Piceatannol; Renoprotection; Resveratrol analogue; Zucker rats