LPS-induced renal inflammation is prevented by (−)‐epicatechin in rats
Paula Denise Prince,
Laura Fischerman,
Jorge E. Toblli,
Cesar G. Fraga,
Monica Galleano
Affiliations
Paula Denise Prince
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analitica y Fisicoquimica, Cátedra de Fisicoquímica, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina
Laura Fischerman
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analitica y Fisicoquimica, Cátedra de Fisicoquímica, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina
Jorge E. Toblli
Laboratorio de Medicina Experimental, Hospital Alemán, Buenos Aires, Argentina
Cesar G. Fraga
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analitica y Fisicoquimica, Cátedra de Fisicoquímica, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina; Department of Nutrition, University of California, Davis, CA 95616, USA
Monica Galleano
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analitica y Fisicoquimica, Cátedra de Fisicoquímica, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina; Corresponding author.
This work investigated the capacity of (−)-epicatechin to prevent the renal damage induced by LPS administration in rats. Male Sprague Dawley rats were fed for 4 days a diet without or with supplementation with (−)-epicatechin (80 mg/kg BW/d), and subsequently i.p. injected with lipopolysaccharide (LPS). Six hours after injection, LPS-treated rats exhibited increased plasma creatinine and urea levels as indicators of impaired renal function. The renal cortex of the LPS-treated rats showed: i) increased expression of inflammatory molecules (TNF-α, iNOS and IL-6); ii) activation of several steps of NF-κB pathway; iii) overexpression of TLR4, and iv) higher superoxide anion production and lipid peroxidation index in association with increased levels of gp91phox and p47phox (NOX2) and NOX4. Pretreatment with dietary (−)-epicatechin prevented the adverse effects of LPS challenge essentially by inhibiting TLR4 upregulation and NOX activation and the consequent downstream events, e.g. NF-kB activation. Keywords: Endotoxemia, Flavonoids, Renopathies, Toll-like receptors, Reactive oxygen species