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Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats

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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.

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Abbreviations

3-NT:

3-nitrotyrosine

ECM:

extracellular matrix

Kim-1:

kidney injury molecule-1

MUFA:

monounsaturated fatty acids

PICEAT:

piceatannol

PUFA:

polyunsaturated fatty acids

ROS:

reactive oxygen species

SFA:

saturated fatty acids

Sirt-1:

sirtuin-1 protein

SOD:

superoxide dismutase

TBARS:

thiobarbituric acid reactive substrates

TGF-β1:

transforming growth factor beta 1

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Acknowledgements

This work was supported by REFBIO Biomedical Network, sustained by the European programme POCTEFA, under the form of a trans-Pyrenean collaborative project: POLYFRESNOL/REFBIO. The authors would like to thank other partners who have participated in the POLYFRESNOL/REFBIO collaborative project: Dr. Luis Bujanda (BioDonostia Institute, San Sebastián, Spain), Dr. José A. Oteo (Hospital San Pedro-CIBIR, Logroño, Spain), Dr. Francoise Nepveu (UPS, Toulouse, France), Dr. Jean Michel Senard (CHUT, Toulouse) and Dr. Anne Bouloumié (INSERM, Toulouse). Prof. Portillo acknowledges the Government of the Basque Country, IT-572-13, and University of the Basque Country (UPV/EHU), ELDUNANOTEK UFI11/32.

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Authors and Affiliations

  1. 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

    Marta Llarena, Fernando Andrade & Luis Aldámiz-Echevarría

  2. Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale (INSERM U1048), Toulouse, France

    Mounia Hasnaoui & Christian Carpéné

  3. 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

    María P. Portillo & Leixuri Aguirre

  4. HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain

    Patricia Pérez-Matute & María Jesús Villanueva-Millán

  5. 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

    Jose M. Arbones-Mainar

  6. 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

    Elizabeth Hijona

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  1. Marta Llarena
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Correspondence to Luis Aldámiz-Echevarría.

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Llarena, M., Andrade, F., Hasnaoui, M. et al. Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats. J Physiol Biochem 72, 555–566 (2016). https://doi.org/10.1007/s13105-015-0457-1

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