(−)-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
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.
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | artículo biblioteca |
| Language: | English |
| Published: |
Elsevier
2018
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| Subjects: | Antioxidant defences, Colonic-derived flavonoid metabolites, Epicatechin, NRK-52E cells, Oxidative injury, Signalling pathways, |
| Online Access: | http://hdl.handle.net/10261/193970 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100000780 |
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