Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells

Abstract

The anti-oxidant effects of epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG)-induced TNF-α and IL-6 production in human embryonic kidney (HEK) cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE) mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.

(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro

“…Based on fluorescence property, we examined the influence of ALA on the formation of total AGEs. Our results demonstrated that ALA efficiently inhibited fructose-induced AGEs formation which supports a previous report on the inhibitory effects of ALA on fluorescent AGEs formation in vivo [ 34 , 35 , 67 ]. The possible mechanism of action of ALA in inhibiting the formation of fluorescent AGEs include: (i) blocking the amino groups of protein, thus preventing its glycation with free sugar, (ii) blocking the carbonyl groups of reducing sugars, (iii) preventing the formation of Amadori products by blocking the Schiff’s base to Amadori products conversion, (iv) blocking the Amadori products and dicarbonyl intermediates which may reduce glycation, as well as AGEs formation, and/or (v) preventing autoxidation of fructose and glycoxidation of Amadori products.…”

“…In obese Zucker rats, chronic treatment of ALA significantly inhibited protein carbonyls content and improved insulin sensitivity in skeletal muscle [ 33 ]. ALA also inhibited AGEs production and down-regulated the receptor for advanced glycation end products (RAGE) expression in streptozotocin-induced diabetic rats [ 34 ] and in human embryonic kidney cells and in rat sensory neurons [ 35 , 36 ]. In addition, topical treatment of ALA nanoparticles significantly down-regulated the expression of RAGE and enhanced cutaneous wound healing in streptozotocin-induced diabetic mice [ 37 ].…”

Attenuation of Glucose-Induced Myoglobin Glycation and the Formation of Advanced Glycation End Products (AGEs) by (R)-α-Lipoic Acid In Vitro

“…Based on fluorescence property, we examined the influence of ALA on the formation of total AGEs. Our results demonstrated that ALA efficiently inhibited glucose-induced AGEs formation which supports our recent paper [ 47 ] and other previously published reports on inhibitory effects of ALA on fluorescent AGEs formation [ 34 , 36 , 59 ]. The possible mechanism of action of ALA in inhibiting the formation of fluorescent AGEs include: (i) blocking the amino groups of protein, thus preventing its glycation with free sugar; (ii) blocking the carbonyl groups of reducing sugars; (iii) preventing the formation of Amadori products by blocking the Schiff’s base to Amadori products conversion; (iv) blocking the Amadori products and dicarbonyl intermediates which may reduce glycation, as well as AGEs formation; and/or (v) preventing autoxidation of glucose and glycoxidation of Amadori products.…”

“…In obese Zucker rats, the chronic treatment of ALA significantly inhibited protein carbonyls content and improved insulin sensitivity in skeletal muscle [ 34 ]. α-Lipoic acid also inhibited AGEs production and down-regulated receptor for advanced glycation end products (RAGE) expression in streptozotocin-induced diabetic rats [ 35 ], in human embryonic kidney cells and in rat sensory neurons [ 36 , 37 ]. The topical treatment of ALA nanoparticles significantly down-regulated the expression of RAGE and enhanced cutaneous wound healing in streptozotocin-induced diabetic mice [ 38 ].…”

Nutrients, Nutraceuticals and Xenobiotics Affecting Renal Health

“…In another very recent study, catechin administration at different dosages after cadmium exposure significantly attenuated the nephrotoxic effects of cadmium exposure by reducing oxidative stress, inflammation and by protecting the renal mitochondrial structure and function [125]. A protective role for EGCG in the development of diabetic nephropathy in mice has also been reported [126][127][128][129][130], by upregulating the nuclear factor erythroid 2-related factor 2 (NRF2), which plays a key role in cellular defence against diabetesinduced oxidative stress [130]. In a double-blind RCT, supplementation with green tea polyphenols containing 800 mg of EGCG was able to reduce albuminuria in patients with diabetic nephropathy receiving the maximum recommended dose of RAS inhibition through a reduction in the podocyte apoptosis by activation of the WNT pathway [131].…”