Activation of NFkB signaling pathway in renal cortex of fructose-fed rats: effects of dietary (?)-Epicatechin

PRINCE, PD; FRAGA, CG; TOBLLI, JE; HID, E; GALLEANO, M

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

Activation of NFkB signaling pathway in renal cortex of fructose-fed rats: effects of dietary (?)-epicatechinPrince PD, Hid E, Toblli JE, Fraga CG, Galleano MKeywords: fructose; kidney; NFkB activation; (?)-epicatechinHigh fructose consumption (HFC) has been associated to deleterious metabolic conditions. In the kidney, high fructose causes alterations that contribute to the development of chronic kidney disease. Among them, inflammation is a key player of renal damage and loss of function. We evaluated the capacity of the flavanol (‒)-epicatechin (EC) in attenuating the NFkB dependant inflammation induced by HFC in the kidney cortex of rats. Male Sprague-Dawley rats were fed standard diet and water (C), standard diet and fructose 10% (p/v) in the drinking water (F) and standard diet with EC (20 mg/kg BW) and the fructose solution (FE) for 8 w. No changes were observed in the expression levels of TLR-4 among the experimental groups. However, the NFkB activation signaling pathway resulted significantly increased in F group respect to C and FE groups, in terms of higher levels of activating phosphorylation in IKKα/β and p65, higher levels of phosphorylation of IkBα in Ser32 and a higher nuclear p65/cytosolic p65 ratio, an indicator of NFkB translocation to the nucleus (+99%*, +41%*; +113%* and +37%* F vs. C). In parallel with these results, F group showed a higher superoxide anion production (+107%* F vs. C) associated with an increased expression of NOX2 and NOX4 subunits, which were not observed in C and FE groups. EC supplementation also attenuated the increased expression of the inflammatory molecules iNOS, TNFα and IL-6 in kidney cortex induced by HFC. Although TLR-4 expression was not altered, a possible activation of this receptor by LPS may be possible, given that in HFC models a higher intestinal permeability is observed. Other TLR-4 independent mechanisms could be responsible for NFkB activation e.g. reticulum stress-induced IKK phosphorylation, triggered by metabolic surplus. This work supports the anti-inflammatory effect of EC, describing its modulation on NFkB signaling pathway in a context of chronic inflammation in rat kidney.*p < 0.05Trabajo seleccionado para exposición oral el ?Simposio XIII SAIC: Metabolismo y Nutrición.?