scholarly journals Anti-receptor Advanced Glycation End Products Decreases Inflammatory Pathways in Retinopathy Diabetics: In vivo Study

2020 ◽  
Vol 8 (A) ◽  
pp. 414-417
Author(s):  
Ramzi Amin ◽  
A. K. Ansyori ◽  
Riani Erna ◽  
Lilianty Fauzi
Keyword(s):  
Diabetic Retinopathy ◽  
Negative Control ◽  
Control Group ◽  
Advanced Glycation ◽  
Experimental Animals ◽  
Retinal Tissue ◽  
White Rats ◽  
Glycation End Products ◽  
End Products

BACKGROUND: Diabetic retinopathy is an emerging microvascular complication of diabetes mellitus and a causes of blindness in individuals between ages 30 and 70 years, which is characterized by increased proliferation of blood vessels, vascular occlusion, angiogenesis, loss of pericytes from retinal capillaries, microaneurysms, retinal bleeding, increased retinal capillary permeability, thickening of capillary basal membranes, and infarcts that affect the retina, induced to permanent blindness. AIM: This study aimed to find the role of receptor advanced glycation end products (RAGE) inhibition in lowering the vascularization process which causes a decrease in retinal function on diabetic retinopathy. MATERIALS AND METHODS: This research was an in vivo experimental study. A total of 30 male Wistar rats (200 ± 20 g) were obtained from Eureka Research Laboratory (Palembang, Indonesia). Experimental animals were placed in cages under controlled conditions (12 h of light/dark cycles with temperatures of 22 ± 1°C and humidity of 40–60%), fed and drank ad libitum. White rats were induced by diabetes mellitus using alloxan at a dose of 120 mg/kgBW, intraperitoneally, accompanied by drinking 10% glucose solution for 140 days. Furthermore, experimental animals were grouped into five groups (at eight animals per group), Group 1: Normal control, Group 2: Negative control (induced diabetics retinopathy and given intravenous aquadest), Group 3: Given anti-RAGE 1 ng/mL, Group 4: Given anti-RAGE 10 ng/mL, and Group 5: Given anti-RAGE 100 ng/mL. Giving anti-RAGE was done in a single dosage and intravitreal. After the rats were sacrificed by intraperitoneal injection of 10% chloral hydrate, the evacuation of the eye’s retinal tissue was then carried out, fixed in a 4% paraformaldehyde buffer for immunohistochemistry examination of the eye’s retinal tissue. Evaluation of the expression of nuclear factor-κβ (NF-kB) and intercellular adhesion molecule-1 (ICAM-1) used Image J Software so that the percentage of NF-kB and ICAM-1 expression would be obtained. RESULTS: Negative control group showed an increase in NF-kB expression in the retinal tissue of diabetic retinopathy rats. Administration of anti-RAGE showed its potential to suppress NF-kB expression in retinal tissue of diabetic retinopathy white rats as well with an increase of anti-RAGE dose from 1 ng/mL to 100 ng/mL. Activation of NF-kB causes activation of the inflammatory cascade, which is characterized by the production of pro-inflammatory cytokines, one of which is ICAM-1. Giving anti-RAGE could suppress the expression of ICAM-1 along with an increase in anti-RAGE dose. CONCLUSION: Anti-RAGE is able to block the inflammatory process, by inhibiting the expression of NF-kB and ICAM-1 in the retinal tissue of diabetics retinopathy in white rats.

scholarly journals Inhibition of Receptor for Advanced Glycation End Products as New Promising Strategy Treatment in Diabetic Retinopathy

2019 ◽  
Vol 7 (23) ◽  
pp. 3921-3924 ◽  
Author(s):  
Irsan Saleh ◽  
Ziske Maritska ◽  
Nita Parisa ◽  
Rachmat Hidayat
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Advanced Glycation End Products ◽  
Negative Control ◽  
Advanced Glycation ◽  
Vegf Expression ◽  
White Rats ◽  
Glycation End Products ◽  
End Products

BACKGROUND: Extensive intracellular and extracellular formation of advanced glycation end-products (AGEs) is considered a causative factor for vascular injury triggered by hyperglycemia in diabetes. The hyperglycemia will cause accumulation of AGEs, damage to pericytes, nerve growth factor (NGF), glial acid fibrillary protein (GFAP) and increase in vascular endothelial growth factor (VEGF). AIM: This study aimed to assess the efficacy of RAGE inhibition in suppressing the development and progression of diabetic retinopathy through modulation of the inflammatory pathway involving NGF, GFAP, and VEGF. METHODS: The design was in vivo experimental study. Thirty white rats were induced with Alloxan monohydrate. Rats were divided into 5 groups, normal, negative control, groups with an anti-RAGE dose of 1 μg/uL, the dose of 10 μg/uL and 100 μg/uL. After 4 weeks of treatment, HbA1c, NGF, and GFAP levels were measured using ELISA. Quantification of VEGF expression was done using the ImageJ® application. Data was expressed with mean ± SD. Independent T-test with ANOVA and Tukey's post hoc was done. RESULTS: RAGE inhibitors yielded a significant decrease in blood glucose and HbA1c levels. VEGF and RAGE expression were reduced in anti-RAGE groups in various doses. Inhibition of RAGE reduced the damage of retinal pericytes, by reducing GFAP and increasing NGF, and reduced the formation of new blood vessels, by decreasing VEGF expression, in diabetic retinopathy. CONCLUSION: Inhibition of receptor for advanced glycation end-products (RAGE) was effective in suppressing the development and progression of diabetic retinopathy.

scholarly journals Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Vascular Events in Type 2 Diabetic Patients

2021 ◽  
Author(s):  
Alejandra Planas ◽  
Olga Simó-Servat ◽  
Cristina Hernández ◽  
Ángel Ortiz-Zúñiga ◽  
Joan Ramón Marsal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Subcutaneous Tissue ◽  
Control Group ◽  
Advanced Glycation ◽  
Vascular Events ◽  
Glycation End Products ◽  
End Products

Abstract BACKGROUND AND AIMS: Vascular events are the main cause of mortality in patients with type 2 diabetes. However, the risk of vascular events is not homogeneous in subjects with type 2 diabetes and, therefore, an early identification of patients at high risk of developing vascular events remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy (DR) and accumulation of advanced glycation end products (AGEs) in subcutaneous tissue can help to identify those patients at high risk of vascular events.MATERIAL AND METHODS: It was a prospective study comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls, matched by age and sex (PRECISED study: ClinicalTrials.gov NCT02248311). The inclusion period began on September 2014 and finished on June 2017. We collected basal features of the subjects, classical cardiovascular risk factors (i.e. age, sex, hypertension, dyslipidemia and coronary artery calcium score [CACs]), presence and degree of DR, and the accumulation of AGEs in subcutaneous tissue using the AGE readerTM device (DiagnOptics Technologies). We followed these subjects until December 2020, collecting any coronary, cerebrovascular or peripheral arterial event.RESULTS: After a follow up of 4.35 ± 1.43 years, a total of 24 vascular events were registered. There was no significant difference regarding age and gender between individuals with type 2 diabetes and the control group. The number of vascular events was higher in type 2 diabetes group than in the control group (12.3% vs. 1.75%). When analysing the risk factors we found that apart from classic risk factors such as age, gender and CACs, subjects with type 2 diabetes and vascular events presented a higher prevalence of DR (47.8% vs. 24.4%; p = 0.018) and AGEs in subcutaneous tissue (63.15% vs 26.71% of values in the higher tertile, p = 0.001). DR and AGEs in subcutaneous tissue remain as independent variables related to the development of vascular events in the Cox proportional hazard multiple regression analysis (HR 2.58, 95%CI 1.14–5.85, p = 0.023, and HR 4.68, 95%CI 1.83–11.96, p = 0.001; respectively).CONCLUSIONS: As we expected, patients with type 2 diabetes have significantly more VE than non-diabetic subjects. Apart from the classic factors such as age, sex and CACs, we observed that the presence of DR and high levels of AGEs in subcutaneous tissue were predictors of vascular events.

scholarly journals Advanced glycation end products induce immature angiogenesis in in vivo and ex vivo mouse models

2020 ◽  
Vol 318 (3) ◽  
pp. H519-H533 ◽  
Author(s):  
Lixian Chen ◽  
Yun Cui ◽  
Bingyu Li ◽  
Jie Weng ◽  
Weiju Wang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Ex Vivo ◽  
Aortic Ring ◽  
Treated Mouse ◽  
Mouse Retina ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Proliferative diabetic retinopathy (PDR) is a progressive disease predominantly involving pathological angiogenesis and is characterized by the development of immature, fragile, and easily hemorrhagic new vessels. Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) play important roles in the progression of diabetic retinopathy. Our previous studies demonstrated that AGEs promoted HUVEC angiogenesis by inducing moesin phosphorylation via RhoA/Rho-associated protein kinase (ROCK) pathway. The aim of this study was to further confirm AGE-induced angiogenesis in vivo and the involvement of RAGE, ROCK, and moesin phosphorylation in this process. We performed the study in an AGE-treated mouse model with various angiogenesis assays in multiple in vivo and ex vivo models. The results demonstrated that AGEs promoted significant neovascularization in whole mount retina and mouse aortic ring of adult and postnatal mice and in Matrigel plug as well, which were consistently accompanied by increased moesin phosphorylation. The increase of AGE-evoked neovascularization and moesin phosphorylation were both attenuated by RAGE knockout or ROCK inhibitor Y27632 administration in mice. We also revealed the pathological characteristics of AGE-promoted angiogenesis by demonstrating the decrease of pericyte coverage and the disarranged endothelial alignment in microvessels. In conclusion, this study provides in vivo evidences that AGEs induce immature angiogenesis by binding to RAGE, activating the RhoA/ROCK signal pathway and inducing moesin phosphorylation. NEW & NOTEWORTHY Advanced glycation end product (AGE)-induced formation of neovessels and phosphorylation of moesin in retina and aortic ring required AGE receptors. AGEs increased neovessels and the phosphorylation of moesin in retina and aortic ring via RhoA/ROCK pathway. AGE-induced immature angiogenesis in AGE-treated mouse retina and aortic ring. The AGE-RAGE axis and moesin could be candidate targets for overcoming relative diseases.

scholarly journals Influence of Dopamine on Fluorescent Advanced Glycation End Products Formation Using Drosophila melanogaster

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 453
Author(s):  
Ana Filošević Vujnović ◽  
Katarina Jović ◽  
Emanuel Pištan ◽  
Rozi Andretić Waldowski
Keyword(s):  
Drosophila Melanogaster ◽  
Advanced Glycation End Products ◽  
Model Organism ◽  
Covalent Modification ◽  
Advanced Glycation ◽  
Biomarkers Of Aging ◽  
Glycation End Products ◽  
End Products

Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.

scholarly journals MiR-92b-3p is Induced by Advanced Glycation End Products and Involved in the Pathogenesis of Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Li-ping Wang ◽  
Jia-nan Geng ◽  
Bo Sun ◽  
Cheng-bo Sun ◽  
Yan Shi ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Rat Kidney ◽  
Luciferase Reporter ◽  
Control Group ◽  
Age Group ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Purpose. The current study aims to examine the effects of advanced glycation end products (AGEs) on the microRNA (miRNA) expression profile in the kidney tissues of rats. Methods. Wistar rats were randomly divided into three equal experiment groups: the AGE group, the RSA group, and the control group. The rats in the AGE group and the RSA group were administered with advanced glycation end products (AGEs) and rat serum albumin (RSA) via the tail vein, respectively, whereas the control group received PBS. Total RNA was prepared from the rat kidney tissues, and the miRNA expression profiles in different experiment groups were compared by microarray analysis. The expression levels of selected differential miRNAs were verified by RT-qPCR. Target gene prediction was conducted using algorithms such as TargetScan, miRanda, and PICTar. Functional analysis was performed to determine the putative biological roles of the validated miRNAs. Results. The microarray study revealed 451 upregulated and 320 downregulated miRNAs in the AGE group compared with the RSA group (p<0.05). Seven miRNAs, including miR-21-5p, miR-92b-3p, miR-140-3p, miR-196a-5p, miR-181b-5p, miR-186-5p, and miR-192-5p, were screened and verified using RT-qPCR, of which, the change of miR-92b-3p was the most obvious according to the miRNA expression different multiple and p value. Furthermore, the expression trend of miR-92b-3p measured by RT-qPCR was shown to be consistent with the microarray results. Bioinformatics analysis and luciferase reporter assay identified Smad7 was a direct target of miR-92b-3p. Both immunohistochemical and western blotting showed that Smad7 expression was significantly suppressed in the kidney tissues from the AGE group compared with the control and RSA groups. Conclusion. The results of the current study suggested that miR-92b-3p could mediate AGE-induced development of renal abnormalities through targeting Smad7 in rats with DN.

Dietary sugars and related endogenous advanced glycation end-products increase chromosomal DNA damage in WIL2-NS cells, measured using cytokinesis-block micronucleus cytome assay

Mutagenesis ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 169-177 ◽  
Author(s):  
Permal Deo ◽  
Caitlin L McCullough ◽  
Theodora Almond ◽  
Emma L Jaunay ◽  
Leigh Donnellan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Advanced Glycation End Products ◽  
Chromosomal Dna ◽  
Advanced Glycation ◽  
Age Related ◽  
Genome Damage ◽  
Glycation End Products ◽  
End Products ◽  
High Concentrations

Abstract This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu–BSA) or with fructose (Fru–BSA). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed higher Nε-carboxymethyllysine (CML; 26.76 ± 1.09 nmol/mg BSA) levels in the Glu–BSA model. Nε-Carboxyethyllysine (CEL; 7.87 ± 0.19 nmol/mg BSA) and methylglyoxal-derived hydroimidazolone-1 (MG-H1; 69.77 ± 3.74 nmol/mg BSA) levels were higher in the Fru–BSA model. Genotoxic effects were measured using CBMN-Cyt assay biomarkers [binucleated(BN) cells with micronuclei (MNi), BN with nucleoplasmic bridges (NPBs) and BN with nuclear buds (NBuds)] following 9 days of treatment with either glucose, fructose, Glu–BSA or Fru–BSA. Fructose treatment exerted a significant genotoxic dose–response effect including increases of BN with MNi (R2 = 0.7704; P = 0.0031), BN with NPBs (R2 = 0.9311; P &lt; 0.0001) and BN with NBuds (R2 = 0.7118; P = 0.0091) on cells, whereas the DNA damaging effects of glucose were less evident. High concentrations of AGEs (400–600 µg/ml) induced DNA damage; however, there was no effect on cytotoxicity indices (necrosis and apoptosis). In conclusion, this study demonstrates a potential link between physiologically high concentrations of reducing sugars or AGEs with increased chromosomal damage which is an important emerging aspect of the pathology that may be induced by diabetes. Ultimately, loss of genome integrity could accelerate the rate of ageing and increase the risk of age-related diseases over the long term. These findings indicate the need for further research on the effects of glycation on chromosomal instability and to establish whether this effect is replicated in humans in vivo.

scholarly journals Advanced Glycation End Products: Formation, Role in Diabetic Complications, and Potential in Clinical Applications

2020 ◽  
Author(s):  
Rujman Khan ◽  
Xin Yee Ooi ◽  
Matthew Parvus ◽  
Laura Valdez ◽  
Andrew Tsin
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Diabetic Complications ◽  
Tanshinone Iia ◽  
Future Research ◽  
Advanced Glycation ◽  
Reactive Aldehydes ◽  
Glycation End Products ◽  
End Products ◽  
Lysine Residues

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic retinopathy but will also explore how they impact other diseases.

scholarly journals Use of Grape Pomace Phenolics to Counteract Endogenous and Exogenous Formation of Advanced Glycation End-Products

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1917 ◽  
Author(s):  
Pedapati S. C. Sri Harsha ◽  
Vera Lavelli
Keyword(s):  
Advanced Glycation End Products ◽  
Grape Pomace ◽  
Advanced Glycation ◽  
Sweetened Beverages ◽  
Glycation End Products ◽  
End Products ◽  
Food Applications ◽  
Double Blinded

The increase in consumption of “ultra-processed” foods has raised attention because of the possible adverse effects deriving from the Maillard reaction leading to the formation of toxic advanced glycation end-products (AGEs) during food processing. Additionally, the increasing trend and consumption of sugar-added foods and sweetened beverages is related to the endogenous formation of the same toxic compounds. However, ultra-processing in the context of food technology can bring challenges as well as a wealth of opportunities. Indeed, re-processing of grape pomace, a by-product of winemaking, can yield phenolic-rich fractions that efficiently counteract the effects of AGEs. In this review, the process of endogenous and exogenous AGE formation is illustrated. Then, the ability of grape phenolics to act as inhibitors of AGE formation is presented, including the efficacy ranking of various individual compounds measured in vitro and the outcome of in vivo double-blinded randomized crossover trials designed to prove the efficacy of grape phenolics as inhibitors of protein carbonylation. Finally, a survey of model functional foods added with grape phenolics, either to lower the dietary load of AGEs or to deliver antiglycation agents in vivo is listed in order to highlight the opportunity to develop safe and tailor-made “anti-AGEs” food applications.

Sign in / Sign up

Export Citation Format

Share Document