Nonenzymatic glycosylation: A biochemical link between chronic hyperglycemia and pathophysiologic processes associated with diabetic complications and aging related debilities

Nimbalkar, Vikram; Mandlik, Rahul; Naik, Suresh R.; Maseeh, Arun

doi:10.1016/j.biomag.2012.08.001

Cited by 5 publications

(5 citation statements)

References 89 publications

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“…The values for both K sv and K a have been tabulated (Table 2). The value of K a for TLB and IBP in the case of native BSA was found to be 2.9 and 2.6 (×10 5 ), which is comparatively higher when compared to the Arg-P (1.4 and 1.2 (×10 5 ) and CEL (1.5 and 1.7 (×10 5 ) modified BSA respectively. Based on the determination of the association constant (K a ) it was evident that the AGEs modified form of BSA exhibited comparatively less affinity for both site I and II specific drugs, i.e., TLB and IBP.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 85%

“…Formation of advanced glycation end products (AGEs) is a key factor in the development of various complications such as Alzheimer’s disease, cataract, Parkinson’s disease and chronic kidney disease . Hyperglycemic conditions where the blood glucose level goes above normal result in increased flux of glucose and its metabolic intermediates toward different pathways contributing to the formation of highly toxic pro-oxidants called AGEs . AGEs are highly heterogeneous compounds which have been classified as fluorescent, nonfluorescent, cross-linking, and non-cross-linking …”

Section: Introductionmentioning

confidence: 99%

“…4 Hyperglycemic conditions where the blood glucose level goes above normal result in increased flux of glucose and its metabolic intermediates toward different pathways contributing to the formation of highly toxic pro-oxidants called AGEs. 5 AGEs are highly heterogeneous compounds which have been classified as fluorescent, nonfluorescent, cross-linking, and non-cross-linking. 6 Figure 1 presents a schematic representation for the nonenzymatic glycation reaction leading to the formation AGEs.…”

Section: ■ Introductionmentioning

confidence: 99%

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Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin

2015

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The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs.

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Section: Molecular Pharmaceuticsmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin

2015

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“…Normal physiologic conditions lead to progressive increase in AGE formation with aging [4]. However, the process is accelerated under hyperglycemic conditions and in other inflammatory diseases [5][6][7][8]. AGEs can even be ingested through food [9].…”

Section: Introductionmentioning

confidence: 99%

Garlic Extract: Inhibition of Biochemical and Biophysical Changes in Glycated HSA

et al. 2021

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Glycation of various biomolecules contributes to structural changes and formation of several high molecular weight fluorescent and non-fluorescent, advanced glycation end products (AGEs). AGEs and glycation are involved in various health complications. Synthetic medicines, including metformin, have several adverse effects. Natural products and their derivatives are used in the treatment of various diseases due to their significant therapeutic qualities. Allium sativum (garlic) is used in traditional medicines because of its antioxidant, anti-inflammatory, and anti-diabetic properties. This study aimed to determine the anti-glycating and AGEs inhibitory activities of garlic. Biochemical and biophysical analyses were performed for in vitro incubated human serum albumin (HSA) with 0.05 M of glucose for 1, 5, and 10 weeks. Anti-glycating and AGEs inhibitory effect of garlic was investigated in glycated samples. Increased biochemical and biophysical changes were observed in glycated HSA incubated for 10 weeks (G-HSA-10W) as compared to native HSA (N-HSA) as well as glycated HSA incubated for 1 (G-HSA-1W) and 5 weeks (G-HSA-5W). Garlic extract with a concentration of ≥6.25 µg/mL exhibited significant inhibition in biophysical and biochemical changes of G-HSA-10W. Our findings demonstrated that garlic extract has the ability to inhibit biochemical and biophysical changes in HSA that occurred due to glycation. Thus, garlic extract can be used against glycation and AGE-related health complications linked with chronic diseases in diabetic patients due to its broad therapeutic potential.

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“…Although glycation is a slow process but increases several folds during persistent hyperglycemia [14], plasma amines react with the carbonyl group of sugars, Amadori products, and RCS, thereby preventing the nucleophilic addition reaction between >C=O and -NH 2 [15]. Furthermore, antioxidants quench glycation-derived ROS, whereas transport proteins such as ceruloplasmin bind with the transition metal ions and prevent them to participate in autoxidation and glycoxidation reactions [16,17]. Aminoguanidine (AG), a hydrazine compound, is an antiglycation drug that inhibits AGE generation via blocking the carbonyl groups on reducing sugars, Amadori products, and RCS [18,19].…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model

Ahmad

Khan

Alouffi

et al. 2021

BioMed Research International

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Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and - N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

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Nonenzymatic glycosylation: A biochemical link between chronic hyperglycemia and pathophysiologic processes associated with diabetic complications and aging related debilities

Cited by 5 publications

References 89 publications

Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin

Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin

Garlic Extract: Inhibition of Biochemical and Biophysical Changes in Glycated HSA

Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model

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