Kidney inflammation: protective action of (-)-epicatechin

PRINCE, PD; GALLEANO, M; FISCHERMAN, L; FRAGA, CG

Québec

Congreso; 8th International Conference on Polyphenols and Health; 2017

International Conference on Polyphenols and Health 2017

The mechanisms of action of flavonoids in terms of their anti-inflammatory effects are not yet fully elucidated. Identifying those mechanisms in becoming crucial given the necessity to identify fruits and vegetables that would benefit health and, for example, to protect kidney function in individuals with renal inflammatory processes. We used two models of kidney inflammation to characterize the anti-inflammatory effects of (‒)-epicatechin (EC). For this purpose, male Sprague-Dawley rats were studied in: i) a model of acute endotoxemia induced by bacterial wall lipopolysaccharide (LPS), and ii) a model of fructose overload. In the endotoxemia model, rats were fed for 4 d a control diet without or with supplementation with 100 mg EC/kg BW/d. At the fourth day, the groups were subdivided into two subgroups, administered i.p. physiological solution or LPS (4 mg/kg BW) and 6 h later rats were euthanized. In the fructose overload model, rats were fed for 8 w with a control diet without or with supplementation of 20 mg EC/kg BW/d, and receiving as beverage water or a solution of 10% (w/v) of fructose. Endotoxemia and fructose overload led to altered renal function associated to inflammation, assessed as increased expression in kidney cortex of inducible nitric oxide synthase (iNOS) and the pro-inflammatory cytokines TNF- and IL-6. NF-κB was activated in kidney cortex in both models as evaluated by increased phosphorylation of IKK α/β and IκBα, and a higher p65 nuclear/cytosolic ratio. All these inflammatory manifestations were prevented or attenuated by the administration of EC. The expression of TLR4 was significantly increased in renal cortex of LPS-treated rats and this effect was not observed in rats treated with EC; whereas TLR4 levels were not affected by any of the treatments in the model of fructose overload. Additionally, EC inhibited the overexpression of NADPH-oxidase subunits induced by LPS and fructose overload in kidney cortex, with the subsequent decrease in the production of oxidants that could activate the NF-κB pathway. These results suggest that the capacity of EC to inhibit the NF-κB pathway can explain in part its anti-inflammatory actions and the restoration of normal kidney function.Supported by grants from the Universidad de Buenos Aires (UBACyT 20020130100760BA and 20020160100132BA); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (PIP0612); and the Packer-Weiss endowment.