Polyphenols Attenuate Highly-Glycosylated Haemoglobin-Induced Damage in Human Peritoneal Mesothelial Cells.

Carolina Sánchez-Rodríguez,Julián Nevado,Concepción Peiró,Leocadio Rodríguez-Mañas

doi:10.3390/antiox9070572

Abstract

We investigated the cytoprotective role of the dietary polyphenols on putative damage induced by Amadori adducts in Human Peritoneal Mesothelial Cells (HPMCs). Increased accumulation of early products of non-enzymatic protein glycation—Amadori adducts—in the peritoneal dialysis fluid due to their high glucose, induces severe damage in mesothelial cells during peritoneal dialysis. Dietary polyphenols reportedly have numerous health benefits in various diseases and have been used as an efficient antioxidant in the context of several oxidative stress-related pathologies. HPMCs isolated from different patients were exposed to Amadori adducts (highly glycated haemoglobin, at physiological concentrations), and subsequently treated with several polyphenols, mostly presented in our Mediterranean diet. We studied several Amadori-induced effects in pro-apoptotic and oxidative stress markers, as well as the expression of several pro-inflammatory genes (nuclear factor-kappaB, NF-kB; inducible Nitric Oxide synthetase, iNOS), different caspase-activities, level of P53 protein or production of different reactive oxygen species in the presence of different polyphenols. In fact, cytoprotective agents such as dietary polyphenols may represent an alternate approach to protect mesothelial cells from the cytotoxicity of Amadori adducts. The interference with the Amadori adducts-triggered mechanisms could represent a therapeutic tool to reduce complications associated with peritoneal dialysis in the peritoneum, helping to maintain peritoneal membrane function longer in patients undergoing peritoneal dialysis.

Highlights

Peritoneal dialysis (PD) is an effective alternative method to haemodialysis in patients with nephropathy and end-stage renal disease (ESRD) [1]
We have shown that Amadori adducts, such as high glycated human haemoglobin (HHb) and glycated bovine serum albumin may favour a pro-inflammatory and pro-apoptotic state in several cell types, such as aortic smooth, endothelial and mesothelial cells (MCs) [9,10,11,12]
We study the effect of treatment with different polyphenols on oxidative stress, apoptosis and inflammation induced by Amadori adducts in Human Peritoneal Mesothelial

Summary

Introduction

Peritoneal dialysis (PD) is an effective alternative method to haemodialysis in patients with nephropathy and end-stage renal disease (ESRD) [1]. During PD, peritoneal dialysis fluids (PDF) have shown cytotoxic effects based on their high glucose and lactate concentrations, the acidic pH, and numerous toxic glucose degradation products (GDP) [2,3]. High concentrations of glucose impair numerous cellular functions [4,5], including inducing non-enzymatic glycation of cell surface and Antioxidants 2020, 9, 572; doi:10.3390/antiox9070572 www.mdpi.com/journal/antioxidants. Non-enzymatic glycation involves the condensation reaction of a sugar with a protein, resulting first in the rapid formation of a Schiff base, after which these adducts undergo rearrangements to stabilize the Amadori adducts. A small portion of these Amadori-adducts undergoes further irreversible chemical reactions leading to the formation of advanced glycation end-products (AGEs) [6,7]. The Amadori adducts or AGE transformation of proteins on the peritoneal barrier, which is formed by mesothelial cells (MCs), induces loss of ultrafiltration capacity and increases membrane permeability to low-molecular-weight solutions [8]

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Conclusion