The anti-inflammatory effect of (‒)-epicatechin(EC) dietary supplementation was evaluated in two animal models with a pro-inflammatory component in the kidney: i) septic inflammation induced by acute lipopolysaccharide (LPS) administration, and ii) chronic fructose overload, that establishes a low-grade systemic inflammation. For the model of septic inflammation, male Sprague-Dawley rats were fed chow diet with or without EC supplementation (80 mg/kg BW). After 4 d, half of the animals receiving EC were administered sterile saline solution i.p. and the other half were administered LPS (4 mg/kg BW) i.p. for 6 h, obtaining the following experimental groups: control (C1); LPS (L); LPS-EC (LE). For the model of metabolic inflammation, male Sprague-Dawley rats received fructose 10% (p/v) in the drinking water for 8 w with or without EC supplementation (20 mg/kg BW), obtaining the following experimental groups: control (C2); fructose (F); fructose-EC (FE). For both
experimental designs, after euthanization the renal cortex was excised and processed for the western blot determinations. LPS and Fructose-treated groups presented a pro-inflammatory profile in renal cortex compared to the control groups, with increased expressions of iNOS, TNFα and IL-6 and the activation of NF-κB signaling pathway, leading to an increased nuclear p65/cytosolic p65 content (86% for L and 37% for F), that is an indicator of an increased translocation of NF-κB to the nucleus. EC dietary administration significantly decreased the expressions of these inflammatory molecules and the activation of NF-κB signaling pathway at different steps. LPS and Fructose-treated rats showed increased ex vivo superoxide anion production (~100% respect to their controls) and increased expressions of NOX4 and p47phox, an activating subunit of NOX2, in renal cortex compared to their respective control groups (NOX4: 61% for F and 47% for L; p47phox: 31% for F and 66% for L). Theses alterations were absent in the groups receiving EC (FE and LE groups). Additionally, TLR-4 expression was studied in kidney cortex of all the animals. Only in L group there was an increased expression in TLR-4 (125% respect to its control), that was absent in the presence of EC in the diet. In conclusion, these results suggest the modulation of NADPH oxidases activity/expression as a key event in the mechanisms involved in the antiinflammatory action of EC. Although more studies are necessary to completely understand the mechanisms finally mediating (−)-epicatechin actions, the presented results reinforce the idea that appropriate dietary components could benefit health, both when an acute inflammation is triggered, and in the cases of systemic lowgrade inflammation. Supported by PIP 11220170100585C (MG), UBACyT