LPS-induced renal inflammation is prevented by (−)‐epicatechin in rats

Prince, Paula D.; Fischerman, Laura; Toblli, Jorge Eduardo; Fraga, César G.; Galleano, Mónica

doi:10.1016/j.redox.2016.12.023

Cited by 73 publications

(44 citation statements)

References 44 publications

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“…In addition, it should be considered that enhanced levels of ROS activate inflammatory mediators and different signalling pathways apart from the mechanisms studied in the present work (Forbes & Cooper, 2013;. In this line, it has been reported that EC is able to prevent the inflammatory response in the kidney through the downregulation of redox-sensitive pro-inflammatory pathways, such as NF-κB, NOX, TNFα, iNOS, and IL-6 (P. D. Prince, Fischerman, Toblli, Fraga, & Galleano, 2017;P. D. Prince et al, 2016).…”

Section: Discussionmentioning

confidence: 81%

(−)-Epicatechin and the colonic metabolite 3,4-dihydroxyphenylacetic acid protect renal proximal tubular cell against high glucose-induced oxidative stress by modulating NOX-4/SIRT-1 signalling

Álvarez-Cilleros

Goya

Ramos

2018

Journal of Functional Foods

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Oxidative stress plays a main role in the pathogenesis of the diabetic nephropathy. The present study investigated the effect of (-)-epicatechin (EC) and the colonic-derived flavonoid metabolites 2,3-dihydroxybenzoic acid, 3,4-dihydroxyphenylacetic acid (DHPAA), and 3-hydroxyphenylpropionic acid on the redox status in high-glucoseexposed renal proximal tubular NRK-52E cells. EC and DHPAA (10µM) alleviated the redox imbalance induced in high-glucose-challenged cells, as both compounds reverted to control levels reactive oxygen species (ROS) values. EC and DHPAA pre-treatment prevented the decrease of antioxidant defences and silent information regulator protein-1 (SIRT-1), and the increase of phosphorylated mitogen-activated-protein-kinases and NADPH-oxidase-4 (NOX-4) values under high-glucose-conditions. The presence of selective NOX-4 and SIRT-1 inhibitors in EC-and DHPAA-pre-treated cells showed the involvement of both proteins in EC-and DHPAA-mediated protection. These findings suggest that EC and DHPAA protected NRK-52E cells against a high-glucosechallenge by improving the cellular redox status through multiple signalling pathways, playing NOX-4/SIRT-1 a relevant role.

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Section: Discussionmentioning

confidence: 81%

(−)-Epicatechin and the colonic metabolite 3,4-dihydroxyphenylacetic acid protect renal proximal tubular cell against high glucose-induced oxidative stress by modulating NOX-4/SIRT-1 signalling

Álvarez-Cilleros

Goya

Ramos

2018

Journal of Functional Foods

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“…This finding open the question whether MORG1 heterozygosity could play a role not only in the HIFs pathway, but as well in the NF-κB signalling path, that is activated through LPS/ TLR4 signalling. Upon LPS or TNF-α stimulation NF-kB is activated in an IKKα,β, depended manner, which phosphorylates IκB-α leading to proteasomal degradation of IκB-α and subsequent liberation, nuclear translocation and activation of the NF-κB complex [ 41 – 43 ]. Indeed, we were able to detect an intact NF-κB signalling path in wild-type LPS treated MORG1 +/+ mice, characterised with an increased phosphorylation levels of IκB-α and IKKα,β, as well as elevated NF-κB nuclear translocation and increased iNOS expression.…”

Section: Discussionmentioning

confidence: 99%

MORG1+/− mice are protected from histological renal damage and inflammation in a murine model of endotoxemia

Bondeva

Schindler

et al. 2018

BMC Nephrol

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BackgroundThe MAPK-organizer 1 (MORG1) play a scaffold function in the MAPK and/or the PHD3 signalling paths. Recently, we reported that MORG1+/− mice are protected from renal injury induced by systemic hypoxia and acute renal ischemia-reperfusion injury via increased hypoxia-inducible factors (HIFs). Here, we explore whether MORG1 heterozygosity could attenuate renal injury in a murine model of lipopolysaccharide (LPS) induced endotoxemia.MethodsEndotoxemia was induced in mice by an intraperitoneal (i.p) application of 5 mg/kg BW LPS. The renal damage was estimated by periodic acid Schiff’s staining; renal injury was evaluated by detection of urinary and plasma levels of neutrophil gelatinase-associated lipocalin and albumin/creatinine ratio via ELISAs. Renal mRNA expression was assessed by real-time PCR, whereas the protein expression was determined by immunohistochemistry or Western blotting.ResultsLPS administration increased tubular injury, microalbuminuria, IL-6 plasma levels and renal TNF-α expression in MORG1+/+ mice. This was accompanied with enhanced infiltration of the inflammatory T-cells in renal tissue and activation of the NF-κB transcription factors. In contrast, endotoxemic MORG1+/− showed significantly less tubular injury, reduced plasma IL-6 levels, significantly decreased renal TNF-α expression and T-cells infiltration. In support, the renal levels of activated caspase-3 were lower in endotoxemic MORG1+/− mice compared with endotoxemic MORG1+/+ mice. Interestingly, LPS application induced a significantly higher accumulation of renal HIF-2α in the kidneys of MORG1+/− mice than in wild-type mice, accompanied with a diminished phosphorylation of IκB-α and IKK α,β and decreased iNOS mRNA in the renal tissues of the LPS-challenged MORG1+/− mice, indicating an inhibition of the NF-κB transcriptional activation.ConclusionsMORG1 heterozygosity protects against histological renal damage and shows anti-inflammatory effects in a murine endotoxemia model through modulation of HIF-2α stabilisation and/or simultaneous inhibition of the NF-κB signalling. Here, we show for the first time that MORG1 scaffold could represent the missing link between innate immunity and inflammation.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-0826-4) contains supplementary material, which is available to authorized users.

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“…In experimental and clinical studies, inflammatory markers such as C-reactive protein, tumor necrosis factor-alpha, interleukin 6 and nu-clear factor kappa-␤, are associated with lipids level [39]. EC has been shown to reduce chronic inflammation in various animal models and under various conditions [17,[40][41][42][43][44]. In current study, EC was found to significantly reduce IL-1beta, IL-2 and IL-6 in hyperlipidemic rats, with is in line with previous reports.…”

Section: Discussionmentioning

confidence: 99%

(‐)‐Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high‐fat diet

Cheng

Zhao

et al. 2017

Molecular Nutrition Food Res

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LPS-induced renal inflammation is prevented by (−)‐epicatechin in rats

Cited by 73 publications

References 44 publications

(−)-Epicatechin and the colonic metabolite 3,4-dihydroxyphenylacetic acid protect renal proximal tubular cell against high glucose-induced oxidative stress by modulating NOX-4/SIRT-1 signalling

(−)-Epicatechin and the colonic metabolite 3,4-dihydroxyphenylacetic acid protect renal proximal tubular cell against high glucose-induced oxidative stress by modulating NOX-4/SIRT-1 signalling

MORG1+/− mice are protected from histological renal damage and inflammation in a murine model of endotoxemia

(‐)‐Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high‐fat diet

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