Formation Of Glycation Products Research Articles

Deciphering the inhibitory mechanisms of betanin and phyllocactin from Hylocereus polyrhizus peel on protein glycation, with insights into their application in bread

Protein glycation closely intertwines with the pathogenesis of various diseases, sparking a growing interest in exploring natural antiglycation agents. Herein, high-purity betacyanins (betanin and phyllocactin) derived from Hylocereus polyrhizus peel were studied for their antiglycation potential using an in vitro bovine serum albumin (BSA)-glucose model. Notably, betacyanins outperformed aminoguanidine, a recognized antiglycation agent, in inhibiting glycation product formation across different stages, especially advanced glycation end-products (AGEs). Interestingly, phyllocactin displayed stronger antiglycation activity than betanin. Subsequent mechanistic studies employing molecular docking analysis and fluorescence quenching assay unveiled that betacyanins interact with BSA endothermically and spontaneously, with hydrophobic forces playing a dominant role. Remarkably, phyllocactin demonstrated higher binding affinity and stability to BSA than betanin. Furthermore, the incorporation of betacyanins into bread dose-dependently suppressed AGEs formation during baking and shows promise for inhibiting in vivo glycation process post-consumption. Overall, this study highlights the substantial potential of betacyanins as natural antiglycation agents.

The Inhibition Mechanisms of Three Structurally Different Salvianolic Acids on the Non-Enzymatic Glycation of Bovine Serum Albumin.

The antiglycation mechanisms of three structurally different salvianolic acids (Sals) including salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and salvianolic acid C (Sal-C) were investigated using the bovine serum albumin (BSA)-fructose model. The results showed that the three compounds could inhibit the formation of glycation products, maintain protein structural stability, mitigate the development of amyloid fibrils and scavenge radicals. Notably, Sal-A possessed the highest anti-glycated activity compared with Sal-B and Sal-C. This may be related to the fact that Sal-A contained the most molecules of caffeic acid (Sal-A, Sal-B, and Sal-C possessing two, one, and zero caffeic acid units, respectively), and caffeic acid played a leading role in the antiglycation properties relative to Danshensu. Moreover, these compounds quenched the intrinsic fluorescence intensity of BSA in a static mode, with the binding constants in the order of Sal-A > Sal-B > Sal-C. Obviously, Sal-A possessed the strongest binding affinity among these compounds, which may be one of the reasons why it exhibited the optimal antiglycation capability. Furthermore, molecular docking demonstrated that the three Sals exerted protective effects on BSA by preventing glycation modification of lysine and arginine residues. These findings would provide valuable insights into the potential application of Sals for alleviating non-enzymatic glycation of protein.

Causes of Infertility in Women with Diabetes: Literature Review

Diabetes Mellitus (DM) is a serious chronic disease, resulting from long-term hyperglycemia can lead to various complications. Complications of DM are associated with changes occurring in blood vessels and nerve fibers. Diabetes can affect a woman's reproductive function and lead to infertility. Decreased fertility in women with DM can be caused by various factors related to this disease. To date, the final mechanisms of reduced reproductive function in these women have not been fully elucidated, but it is known that the leading role belongs to chronic hyperglycemia. Purpose: Based on these literature sources, to investigate the possible causes of infertility in women with diabetes. Object: reduced fertility in women as a result of diabetes. Research methods: a review of literary sources. Results: There are quite a few causes of infertility and reduced fertility in women with DM, these include complications of diabetes (diabetic polyneuropathy); insulin resistance and, as a result, polycystic ovary syndrome; obesity; autoimmune and genetic factors; disorders of the menstrual cycle and hormone balance; low quality of egg cells due to oxidative stress and the formation of glycation products; reduction of cervical mucus due to hormonal disbalance, dehydration and inflammatory processes of the genital organs; psychogenic factors (phobias, fear of childbirth, future changes both in the body and in life). Conclusions: Based on the study of literary data, it can be said that the main causes of infertility in women with DM are caused by chronic hyperglycemia, and as a result, the development of pathological conditions that lead to disorders in the reproductive system. In addition, the causes of infertility in women with DM include disorders of the menstrual cycle and hormone balance, polycystic ovary syndrome, obesity, and autoimmune and genetic mechanisms. Taking this into account, glycemic control, prevention and treatment of diabetes complications, lifestyle modification, nutrition, and psychological health support are necessary.

Epigenetic changes underlie the association between diabetes mellitus and oral diseases.

Patients with diabetes mellitus (DM) suffer from oral complications related to oral infections, periodontal diseases, and endodontic lesions. Emerging evidence has revealed the contribution of the epigenetic process as the underlying mechanism of DM complications. DNA methylation, histone modifications, and non-coding RNAs are epigenetic regulators that directly affect gene expression. The present review elaborated on the role of epigenetic dysregulation in the etiology of diabetes-related periodontal and endodontic diseases. The narrative review study was prepared using databases such as PubMed, Google Scholar, Science Direct, and Scopus. The formation of glycation products as a result of hyperglycemic condition increases oxidative stress, and elevates chronic inflammatory mediators that could in turn adversely change the cellular environment and alter the epigenetic status. This process contributes to the alteration of regulatory genes expression, leading to the development of diabetes-induced bone complications and impaired odontogenic capacity of pulp. Indeed, epigenetic mechanisms mediate the interaction between gene expression and DM cellular environment. Further investigations on epigenetic factors involved in DM oral complications may provide novel therapeutic targets.

Suppression of COX-2/PGE2 levels by carbazole-linked triazoles via modulating methylglyoxal-AGEs and glucose-AGEs – induced ROS/NF-κB signaling in monocytes

Chronic hyperglycemia favours the formation of advanced glycation end products (AGEs) which are responsible of many diabetic vascular complications. Keeping in view the medicinal properties of the1,2,3-triazole-conjugated analogs, the present study was designed to evaluate the possible effect of carbazole-linked 1,2,3-triazoles 2–16 against glucose- and methylglyoxal-AGEs-induced inflammation in human THP-1 monocytes. In vitro antiglycation, and metabolic assays were used to determine antiglycation, and cytotoxicity activities. DCFH-DA, immunostaining, immunoblotting, and ELISA techniques were employed to study the ROS and levels of proinflammatory mediators in THP-1 monocytes. Among all the synthesized carbazole-linked 1,2,3 triazoles, compounds 2, 7, 8, and 11–16 showed antiglycation activity in glucose- and MGO-modified bovine serum albumin models, whereas parent compound 1 only exhibited activity in glucose-BSA model. The metabolic assay demonstrated the non-toxic profile of compounds 1–2, 11–13, and 15 up to 100 μM concentration in both HepG2 and THP-1 cell lines. We found that compounds 11–13, and 15 attenuated AGEs-induced ROS formation (P < 0.001), and halted NF-ĸB translocation (P < 0.001), likewise standard drugs, PDTC, rutin, and quercetin, in THP-1 monocytes. Among the derivatives, compounds 12, and 13 also suppressed the AGEs-induced elevation of COX-2 (P < 0.001) and PGE2 (P < 0.001). Our data show that the carbazole-linked triazoles 12, and 13 hampering the formation of glycation products, prevent the activation of AGEs-ROS-NF-κB signaling pathway, and limit the proinflammatory COX-2 protein, and PGE2 induction in human THP-1 monocytes. Both these compounds can thus serve as leads for further studies towards the treatment and prevention of diabetic vascular complications.

Determining the amount and bioaccessibility of methylglyoxal and glyoxal in functional snack foods with herbal teas: effect of different herbal teas on α-Dicarbonyls

The global challenge against cardiovascular diseases, some tumours, diabetes, and diabetes-related disorders have accelerated. These conditions are often due to several dysfunctions in the metabolic pathway, which are influenced by diet. One reason for this is that excess consumption of processed foods may be accompanied by conversion of their components into harmful macromolecules such methylglyoxal (MGO) and glyoxal (GO) in the body. These hazardous compounds can be restricted during metabolism by plant-based natural sources or some medications. In this paper, anti-diabetic beverages such as green tea, bergamot-flavored black tea, and olive-leaf tea were used as plant-based sources, and functional snacks were developed using these ingredients. According to the results, the teas limited the formation of glycation products, with the greatest effects from bergamot-flavored black tea, followed by green tea and olive-leaf tea, respectively. The rates of MGO reduction were 83.80 ± 4.19, 97.84 ± 4.4, and 96.51 ± 4.37 µg/100 g, while the rates of GO reduction were 65.18 ± 2.95, 93.7 ± 4.2, and 33.1 ± 1.50 µg/100 g, respectively.

Effect of unsaturated fatty acids on glycation product formation pathways

Glycation and lipid oxidation in high-nutrient foods are closely related and exhibit complex interactions. To evaluate the effect of unsaturated fatty acids (UFAs) on glycation pathways, glycation products in glucose-lysine-UFA models were detected by ultra performance liquid chromatography-tandem mass spectrometry and electron spin resonance spectroscopy, together with multivariate data analysis. Results indicated that UFAs inhibited glucose oxidation by decreasing the contents of carbonyl compounds about 73.85–86.19%. UFAs promoted the formation of glycation products mainly via production of active radical. In three models, linoleic acid (LA) exhibits stronger glycation activity than oleic acid and eicosapentaenoic acid. LA significantly promoted radical formation, as well as the formation and degradation of fructosyllysine (FL), the signal intensity of active radical increased 647.45% and FL increased 78.73%. The comparison of E(k3), E(k7) and variable importance in projection values of orthogonal projections to latent structures discriminant analysis in three models also proved these conclusions. By studying the characteristics of LA on glycation in three UFA, we hypothesized that unsaturation is not the key factor in evaluating their effects on glycation, the radical activity, UFA solubility, spatial structure and interaction should be considered as potentially important factors.

Current trends in management of hyperglycaemia in surgical patients with diabetes mellitus: a review

A large amount of clinical evidences demonstrates a clear association between long-term and/or stress-related hyperglycaemia, and development of complications after surgery. The incidences of perioperative hyperglycaemia are demonstrated in 20–80 % of all cases depending on the type of elective surgery, with the highest rate registered in cardiac surgery. The most studied pathophysiological complications of long-term hyperglycaemia in Diabetes Mellitus (DM) patients are; activation of the polyol pathway, diacylglycerol/protein kinase C and hexosamine pathways, advanced glycation product formation, and oxidative stress. The uncontrolled stress-related hyperglycaemia during and after surgery instigates: osmotic diuresis with further fluid and electrolyte imbalance, increased gluconeogenesis and glucogenolysis, breakdown of fats into free fatty acid and glycerol, proteins into amino acids, and increases generation of pro-inflammatory cytokines. All these changes may lead to development of diabetic ketoacidosis, immune deregulation and insulin resistance. Some clinical investigations seems to indicate that anaesthesia with propofol may have some advantages in keeping stable blood sugar over inhalational agents. Two clinical trials comparing the influence of different anaesthetic agents on perioperative glycaemic status in diabetic patients are currently underway. For better management of perioperative hyperglycaemia in diabetic patients under surgery we have proposed several important practical principles.&#x0D; &#x0D;

Experimental and theoretical insight into resistance to glycation of bovine serum albumin

Serum albumin is the most abundant protein in plasma and is highly sensitive to glycation, leading to functional and structural alterations. These changes are subsequently involved in the pathophysiological events in diabetes. In this study, our aim is to investigate the formation of glycation products, structural alterations as well as to gain insight into the resistance to glycation using various inhibitors. Bovine serum albumin (BSA) was incubated with a constant glucose concentration (0.05M) for 10 weeks at 37°C. Early, intermediary and advanced glycation end-products (AGEs) were estimated and the glycation induced structural changes were analysed. Complementary shape-based docking studies were carried out to supplement the experimental findings. Significant amounts of ketoamines, protein bound carbonyl content and AGE (pentosidine) were detected in in vitro glycation reactions of BSA. Glycation inhibition studies showed no appreciable change in ketoamine formation. However, significant inhibition in the formation of protein bound carbonyl content and pentosidine in the presence of aminoguanidine and Metformin were observed. Fluorescence study exhibited quenching of tryptophan-based emission and UV absorption of glycated BSA (G-BSA) compared to native BSA (N-BSA). Appreciable changes in secondary structures (α-helix, β-sheet, β-turn and random coils) were observed in G-BSA with aminoguanidine and Metformin. It was also noticed that the effect of Metformin and aminoguanidine drugs was reduced upon BSA with amino acid(s) modification. On the other hand, native BSA exhibited higher binding affinities and stronger binding interactions with both drugs. Aminoguanidine and Metformin exhibited substantial resistance to the formation of intermediary and AGE (pentosidine) molecules, as well as against secondary structural alterations. Hence these agents may protect the integrity and functionality of serum proteins and possibly contribute to reduction of pathophysiological complications in diabetes.

Effect of unsaturated fatty acids on glycation product formation pathways (Ⅰ) the role of oleic acid

Research on advanced glycation end-products (AGEs) and their formation pathways in food processing has gradually increased because AGEs are associated with human health, especially with involvement of lipids. In this study, radicals and glycation products were detected via electron spin resonance (ESR) and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) respectively. The correlation of important intermediates was used to explain the effect of oleic acid (OA) on the glycation products and pathways. The results indicated OA participation decreased the content of stable radicals and glycosyl compounds in Maillard Reaction (MR). The oxidation of OA produced active radicals, and electron transfer caused lysine to transform radical form. These radicals participated in the formation of fructosyllysine (FL) with glucose (Glc) via the MR. The participation of OA is acted as inhibiting the way of Glc autoxidation and promoting the glycation pathway from FL to 3-deoxyglucosone (3-DG) to fluorescent-AGEs. Orthogonal projection to latent structures discriminant analysis results indicated that 3-DG, D-glucosone and methylglyoxal are key products in discriminating the glycation reaction.

Influence of Hydroxyl Substitution on the Suppression of Flavonol in Harmful Glycation Product Formation and the Inhibition Mechanism Revealed by Spectroscopy and Mass Spectrometry.

Quercetin (Que), kaempferol (Kaem), isorhamnetin (Irh), and myricetin (Myri) are typical flavonols that are abundant in plant resources. This research investigated their ability in attenuating harmful glycation product formation and the effect of hydroxyl substitution. The inhibition mechanisms were elucidated by fluorescence spectroscopy and nano-liquid chromatography Orbitrap tandem mass spectrometry. The results indicated that the 3'-OH on the B-ring is critical in alleviating harmful glycation product formation, methylation reduced its inhibition, and the 5'-OH showed much less contribution than the 3'-OH. Que showed the strongest suppression on initial product, 5-hydroxymethylfurfural, and advanced glycation end product formation, with the corresponding percentage inhibitions at 36.58 μM of 81.1, 56.9, and 95.4%. Que and Myri also clearly inhibited fructosamine and acrylaminde production, while no suppression was observed by Irh and Kaem. The number of glycated sites was reduced from ten to seven, five, six, and nine, respectively, when 36.58 μM Que, Myri, Kaem, and Irh was added. Suppressing the conformational changes of ovalbumin induced by glycation, trapping dicarbonyl compounds, altering the microenvironment around tryptophan, and reducing the glycation activity of potential sites were the major inhibition mechanisms. These results suggest that Que and Myri may be promising natural agents for inhibiting harmful glycation and provide theoretical support for the effective screening of natural antiglycation reagents.

Carbamylation and glycation compete for collagen molecular aging in vivo

Tissue aging is a complex phenomenon involving molecular aging of matrix proteins, which mainly results from their progressive alteration by nonenzymatic post-translational modifications (NEPTMs) such as glycation and carbamylation. These two reactions, which correspond to the binding of reactive metabolites (i.e. reducing sugars and urea-derived cyanate, respectively) on amino groups of proteins, occur during aging and are amplified in various chronic diseases such as diabetes mellitus or chronic renal disease (CKD). Since these reactions target the same functional groups, they can reciprocally compete for protein modification. Determining which NEPTM is predominant in tissues is necessary to better understand their role in the development of long-term complications of chronic diseases. For that purpose, two different murine models were used for reproducing such a competitive context: a CKD-diabetic mice model and a cyanate-consuming mice model. The competition has been evaluated by quantifying glycation and carbamylation products by LC-MS/MS in skin and aorta total extracts as well as in skin type I collagen. The results showed that the simultaneous enhancement of glycation and carbamylation reactions resulted in a decrease of the formation of glycation products (especially Amadori products) whereas the concentrations of homocitrulline, a carbamylation product, remained similar. These results, which have been obtained in both tissues and in purified skin type I collagen, suggest that carbamylation takes precedence over glycation for the modification of tissue proteins, but only in pathological conditions favouring these two NEPTMs. While glycation has been considered for a long time the predominant NEPTM of matrix proteins, carbamylation seems to also play an important role in tissue aging. The existence of competition between these NEPTMs must be taken into account to better understand the consequences of molecular aging of matrix proteins in tissue aging.

Inhibition of the Maillard Reaction by Phytochemicals Composing an Aqueous Coffee Silverskin Extract via a Mixed Mechanism of Action.

This work aimed to evaluate the contribution of isoflavones and melatonin to the aqueous extract obtained from the coffee silverskin (CSE) antiglycative properties, which has not been previously studied. To achieve this goal, two model systems constituted by bovine serum albumin (BSA) and reactive carbonyls (glucose or methylglyoxal) in the presence or absence of pure phytochemicals (chlorogenic acid (CGA), genistein, and melatonin) and CSE were employed. Glucose was used to evaluate the effect on the formation of glycation products formed mainly in the early stage of the reaction, while methylglyoxal was employed for looking at the formation of advanced products of the reaction, also called methylglyoxal-derivative advanced glycation end products (AGE) or glycoxidation products. CGA inhibited the formation of fructosamine, while genistein and melatonin inhibited the formation of advanced glycation end products and protein glycoxidation. It was also observed that phenolic compounds from CSE inhibited protein glycation and glycoxidation by forming BSA–phytochemical complexes. CSE showed a significant antiglycative effect (p < 0.05). Variations in the UV-Vis spectrum and the antioxidant capacity of protein fractions suggested the formation of protein–phytochemical complexes. Fluorescence quenching and in silico analysis supported the formation of antioxidant–protein complexes. For the first time, we illustrate that isoflavones and melatonin may contribute to the antiglycative/antiglycoxidative properties associated with CSE. CGA, isoflavones, and melatonin composing CSE seem to act simultaneously by different mechanisms of action.

Anti-glycation activity of curcumin

Curcumin, a compound belonging to the group of polyphenols with a characteristic yellow-orange color, is the most active ingredient of the long-leaved Curcuma longa L. and the ingredient of seasoning mixes, including curry spices. Due to its antioxidant, anti-inflammatory and anti-cancer properties, it has a wide range of therapeutic effects and has been studied for many years. Curcumin has enormous potential in preventing many diseases due to the widely described benefits of its use, it is non-toxic and additionally. Therapy with curcumin is low cost. Currently, many studies focus on the anti-glycation activity of curcumin, which could be used as an active inhibitor of glycation, i.e. a non-enzymatic process of combining a keto or aldehyde group of sugar with a free amino group of a protein. Finally, heterogeneous end products of advanced glycation are formed in the multistage and complicated glycation reaction. Formation of glycation products is intensified with age, as well as in various disease states, including diabetes or neurodegenerative diseases. Many literature data describe the role of curcumin in the prevention and treatment of diabetes. It is known that polyphenol has beneficial effects on hyperglycemia, insulin resistance and regeneration of secretory cells of pancreatic islets. It seems that addition of curcumin, the main ingredient of curry spice, to food could help people prevent the development of lifestyle diseases, including diabetes and its complications. The article presents the current state of knowledge on the curcumin anti-glycation properties in vitro as well as in vivo.

Main anthraquinone components in Aloe vera and their inhibitory effects on the formation of advanced glycation end-products

Food heating process causes increased protein glycation and the formation of advanced glycation endproducts (AGEs) which related with diabetes and ageing. Aloe vera (A. vera) extract is a potent antioxidant with established effects attributed largely to a key ingredient anthraquinone. This study investigated the inhibitory ability of the three anthraquinones from A. vera on the formation of AGEs in a heated model system at 70°C. Anthraquinones, including aloe-emodin (AED), emodin (ED), and chrysophanol (CSN), were extracted from A. vera and analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. Under optimal extraction conditions, the extraction yield of the anthraquinones was 4.377 mg/g. Anthraquinones showed good inhibition toward the formation of glycation products; the inhibition rates of AED, ED, and CSN on crosslinked AGEs were 46.48%, 66.38%, and 57.32% at 10 μM concentrations. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis images also proved that the anthraquinones could significantly inhibit crosslinked AGE formation in a time-dependent manner. ED showed higher inhibitory ability than AED and CSN on the formation of Nɛ-(carboxymethyl)lysine and crosslinked AGEs. The results indicate that the antiglycation properties of these anthraquinones are likely related to the phenolic hydroxyl groups in their structures, but this ability is not related to their antioxidant activity, which probably depends on the whole structure of the quinone. Generally, the anthraquinones in A. vera, especially ED, can effectively inhibit AGE formation and reduce protein crosslinking during food processing, even at low concentration. Practical applications The inhibitory effects of three anthraquinones extracted from Aloe vera on the formation of AGEs were investigated in a heated model system. The results indicate Aloe can be used as an effective inhibitor of glycation products in food processing, moreover, this research can be useful for finding suitable nature inhibitors of AGEs for food processing.

Peel of araticum fruit (Annona crassiflora Mart.) as a source of antioxidant compounds with α-amylase, α-glucosidase and glycation inhibitory activities

Annona crassiflora Mart., whose fruit is popularly known as araticum, is a member of the Annonaceae family found in the Brazilian Cerrado. Although this plant has several medicinal uses, its bioactive molecules are not fully understood. A bioguided assay was performed to identify the main bioactive compounds of A. crassiflora fruit peel from the ethanol extract fractions with antioxidant capacity and α-amylase, α-glucosidase and glycation inhibitory activities. Ethyl acetate and n-butanol fractions showed, respectively, higher antioxidant capacity (DPPH IC50 1.5±0.1 and 0.8±0.1μgmL−1, ORAC 3355±164 and 2714±79μmoltroloxeq/g, and FRAP 888±16 and 921±9μmoltroloxeq/g) and inhibitory activities against α-amylase (IC50 4.5±0.8 and 1.7±0.3μgmL−1), α-glucosidase (IC50 554.5±158.6 and 787.8±140.6μgmL−1) and glycation (IC50 14.3±3.3 and 16.0±4.2μgmL−1), and lower cytotoxicity, compared to the other fractions and crude ethanol extract. The HPLC-ESI-MS/MS analysis identified various biomolecules known as potent antioxidants, such as chlorogenic acid, (epi)catechin, procyanidins, caffeoyl-hexosides, quercetin-glucosides and kaempferol. The fruit peel of A. crassiflora, a specie from Cerrado, the Brazilian Savanna, provided a source of antioxidant compounds with properties to block carbohydrate digestive enzymes and formation of glycation products. Thus, there is potential to use the by-products of araticum in order to identify and isolate phytochemicals for application in nutraceutical supplements, food additives and pharmaceuticals products.

Effect of some high consumption spices on hemoglobin glycation.

Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes.

Glycoxidation of biological macromolecules: a critical approach to halt the menace of glycation.

Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively.

Glycoxidative damage to human DNA: Neo-antigenic epitopes on DNA molecule could be a possible reason for autoimmune response in type 1 diabetes

Advanced glycation end-products (AGEs) are known to be mutagenic, diabetogenic and vascular disease risk factors. Methylglyoxal (MG) is a dicarbonyl species that reacts with biological macromolecule (proteins, DNA and lipids) to give AGEs. Nonenzymatic glycation of MG with lysine (Lys) in the presence of copper (Cu(2+)) is reported to generate reactive oxygen species (ROS) capable of causing DNA damage. We show that DNA modification in MG-Lys-Cu(2+) system results in the generation of strand breaks, base modification, hyperchromicity and increased fluorescence intensity. Superoxide generation in the MG-Lys system was found to be significantly higher when compared with that in the MG and Lys alone. Moreover, d-penicillamine and pyridoxal phosphate significantly inhibited the formation of glycation products. The presence of a major DNA glycation adduct, N(2)-carboxyethyl-2'-deoxyguanosine (CEdG), was detected by high performance liquid chromatography (HPLC) and confirmed by nuclear magnetic resonance (NMR). As reported earlier, modified DNA (MG-Lys-Cu(2+)-DNA) was highly immunogenic in experimental animals. Furthermore, induced anti-MG-Lys-Cu(2+)-DNA antibodies were effective probe for detecting glycoxidative lesions in human genomic DNA of type I diabetes patients. Our results clearly imply that interaction of MG-Lys and Cu(2+) leads to the formation of AGEs and also the production of potent ROS, capable of causing DNA damage, thereby playing an important role in diabetes mellitus.

Faox enzymes inhibited Maillard reaction development during storage both in protein glucose model system and low lactose UHT milk

Fructosamines, also known as Amadori products, are formed by the condensation of glucose with the amino group of amino acids or proteins. These compounds are precursors of advanced glycation end products (AGEs) that can be formed either endogenously during aging and diabetes, and exogenously in heat-processed food. The negative effects of dietary AGEs on human health as well as their negative impact on the quality of dairy products have been widely described, therefore specific tools able to prevent the formation of glycation products are needed. Two fructosamine oxidase enzymes isolated from Aspergillus sp. namely, Faox I and Faox II catalyze the oxidative deglycation of Amadori products representing a potential tool for inhibiting the Maillard reaction in dairy products. In this paper, the ability of recombinant Faox I and II in limiting the formation of carboxy-methyl lysine (CML) and protein-bound hydroxymethyl furfurol (b-HMF) in a commercial UHT low lactose milk and a beta-lactoglobulin (β-LG) glucose model system was investigated. Results show a consistent reduction of CML and b-HMF under all conditions. Faox effects were particularly evident on b-HMF formation in low lactose commercial milk. Peptide analysis of the β-LG glucose system identified some peptides, derived from cyanogen bromide hydrolysis, as suitable candidates to monitor Faox action in milk-based products. All in all data suggested that non-enzymatic reactions in dairy products might be strongly reduced by implementing Faox enzymes.