title: LPS-induced renal inflammation is prevented by (-)-epicatechin in rats.
abstract: 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 (80mg/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 gp91phoxand 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.
authors.affiliation: 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.
authors.forename: Paula Denise
authors.initials: PD
authors.lastname: Prince
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Fischerman
authors.affiliation: Laboratorio de Medicina Experimental, Hospital Alemán, Buenos Aires, Argentina.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Toblli
authors.affiliation: 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.
authors.forename: Cesar G
authors.initials: CG
authors.lastname: Fraga
authors.affiliation: 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. Electronic address: mgallean@ffyb.uba.ar.
authors.forename: Monica
authors.initials: M
authors.lastname: Galleano
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D005786:Gene Expression Regulation; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D000074662:NADPH Oxidase 2 / Q000235:genetics / Q000276:immunology; D000074663:NADPH Oxidase 4 / Q000235:genetics / Q000276:immunology; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009393:Nephritis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014508:Urea / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; D014508:Urea; D003404:Creatinine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C060505:neutrophil cytosolic factor 1
keywords: Endotoxemia; Flavonoids; Reactive oxygen species; Renopathies; Toll-like receptors