Abstract
The renal accumulation of advanced glycation end products (AGEs) is a causative factor of various renal diseases, including chronic kidney disease and diabetic nephropathy. AGE inhibitors, such as aminoguanidine and pyridoxamine, have the therapeutic activities for reversing the increase in renal AGE burden. This study evaluated the inhibitory effects of ethyl pyruvate (EP) on methylglyoxal- (MGO-) modified AGE cross-links with proteins in vitro. We also determined the potential activity of EP in reducing the renal AGE burden in exogenously MGO-injected rats. EP inhibited MGO-modified AGE-bovine serum albumin (BSA) cross-links to collagen (IC50 = 0.19 ± 0.03 mM) in a dose-dependent manner, and its activity was stronger than aminoguanidine (IC50 = 35.97 ± 0.85 mM). In addition, EP directly trapped MGO (IC50 = 4.41 ± 0.08 mM) in vitro. In exogenous MGO-injected rats, EP suppressed AGE burden and MGO-induced oxidative injury in renal tissues. These activities of EP on the MGO-mediated AGEs cross-links with protein in vitro and in vivo showed its pharmacological potential for inhibiting AGE-induced renal diseases.
Highlights
Advanced glycation end products (AGEs) are generated in the human body and affect the function and structure of proteins
To investigate the role of ethyl pyruvate (EP) as a potential AGE inhibitor, we tested whether EP can chelate MGO in vitro
Previous researches have revealed that AGEs play a crucial role in the pathogenic processes of various diseases including Alzheimer’s disease, cardiovascular diseases, and diabetes [31,32,33,34]
Summary
Advanced glycation end products (AGEs) are generated in the human body and affect the function and structure of proteins. AGEs naturally formed low levels in the body by protein or lipid glycation with sugars, and most of them are catabolized depending on the tissue anti-oxidative systems, macromolecular turnover, receptormediated degradation, and renal elimination [2]. AGE formation is an irreversible reaction, and it can be cross-linked with proteins resulting in disturbed biological reaction; AGEs, are implicated in the pathogenic processes of various age-related diseases [3]. Matrix proteins such as collagen are properly cross-linked with AGEs in conditions of diabetes and aging [4, 5]
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