Berry fruits modulate kidney dysfunction and urine metabolome in Dahl salt-sensitive rats

Abstract

Berries are rich sources of (poly)phenols which have been associated with the prevention of cardiovascular diseases in animal models and in human clinical trials. Recently, a berry enriched diet was reported to decrease blood pressure and attenuate kidney disease progression on Dahl salt-sensitive rats. However, the relationship between kidney function, metabolism and (poly)phenols was not evaluated. We hypothesize that berries promote metabolic alterations concomitantly with an attenuation of the progression of renal disease. For that, kidney and urinary metabolomic changes induced by the berry enriched diet in hypertensive rats (Dahl salt-sensitive) were analyzed using liquid chromatography (UPLC-MS/MS) and 1H NMR techniques. Moreover, physiological and metabolic parameters, and kidney histopathological data were also collected. The severity of the kidney lesions promoted in Dahl rats by a high salt diet was significantly reduced by berries, namely a decrease in sclerotic glomeruli. In addition, was observed a high urinary excretion of metabolites that are indicators of alterations in glycolysis/gluconeogenesis, citrate cycle, and pyruvate metabolism in the salt induced-hypertensive rats, a metabolic profile counteracted by berries consumption. We also provide novel insights that relates (poly)phenols consumption with alterations in cysteine redox pools. Cysteine contribute to the redox signaling that is normally disrupted during kidney disease onset and progression. Our findings provide a vision about the metabolic responses of hypertensive rats to a (poly)phenol enriched diet, which may contribute to the understanding of the beneficial effects of (poly)phenols in salt-induced hypertension.

CB, CNS, CO were funded by Agence Nationale de la Recherche (ANR) (ANR-13-ISV1-0001-01) and Fundação para a Ciência e Tecnologia (FCT) (FCTANR/BEX-BCM/0001/2013). We also acknowledge the Investment for the Future program ANR-11-IDEX-0003-01 within the LABEX ANR-10-LABX-0033 (CB, CO), FCT financial support of AG (SFRH/BD/103155/2014). iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by FCT through national funds, and by FEDER under the PT2020 Partnership Agreement is acknowledged. CERMAX - Centro de Ressonância Magnética António Xavier, located within ITQB for the (1H) NMR spectroscopy on an 800 MHz Bruker AvanceII+ funded by FCT project AAC 01/SAICT/2016 and ONEIDA (LISBOA-01-0145-FEDER-016417) which is co-funded by FEEI - “Fundos Europeus Estruturais e de Investimento” from “Programa Operacional Regional Lisboa 2020″ and by national funds from FCT.