(−)-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. (July 2018)

• Record Type: Journal Article
• Authors: Álvarez-Cilleros, David; Martín, María Ángeles; Goya, Luis; Ramos, Sonia
• Is Part Of: Journal of functional foods. Volume 46(2018)
• Page Start: 19
• Page End: 28
• Publication Date: 2018-07
• Subjects: Antioxidant defences -- Colonic-derived flavonoid metabolites -- Epicatechin -- NRK-52E cells -- Oxidative injury -- Signalling pathways; CAT catalase -- DHBA 2, 3-dihydroxybenzoic acid -- DHPAA 3, 4-dihydroxyphenylacetic acid -- DPI diphenyleneiodonium -- EC (−)-epicatechin -- ERK extracellular-regulated kinase -- FBS foetal bovine serum -- GPx glutathione peroxidase -- GR glutathione reductase -- GSH glutathione -- HPPA 3-hydroxyphenilpropionic acid -- JNK c-jun amino-terminal kinase -- MAPKs mitogen-activated protein kinases -- NOX NADPH oxidases -- SIRT-1 silent information regulator protein-1 -- SOD superoxide dismutase -- t-BOOH tert-butylhydroperoxide; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2018.04.051
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: (−)-Epicatechin (EC) and 3, 4-dihydroxyphenilacetic acid (DHPAA) reduce ROS generation. EC and DHPAA alleviated impaired antioxidant defenses in high-glucose-treated- cells. EC- and DHPAA-induced protective effect involves multiple signalling routes. NOX-4/SIRT-1 modulation induced by EC and DHPAA contribute to the redox balance. Abstract: 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-glucose-exposed renal proximal tubular NRK-52E cells. EC and DHPAA (10 µM) 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-glucose-challenge by improving the cellular redox status through multiple signalling pathways, playing NOX-4/SIRT-1 a relevant role.