The Role of Oxidative Stress, Inflammation, and Advanced Glycation End Product in Skin Manifestations of Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Lili Legiawati
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Skin Disorders ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
High Level ◽  
Factor Α

: Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non-T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen-activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

scholarly journals Resveratrol prevents TNF-α-induced VCAM-1 and ICAM-1 upregulation in endothelial progenitor cells via reduction of NF-κB activation

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094513
Author(s):  
Yefei Zhang ◽  
Huahua Liu ◽  
Weiliang Tang ◽  
Qiongya Qiu ◽  
Jiahao Peng
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adhesion Molecule ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Progenitor ◽  
Tnf Α ◽  
Factor Α

Objective To assess the effects of resveratrol (RSV) on expression of adhesion molecules in endothelial progenitor cells (EPCs) following tumor necrosis factor-α (TNF-α) stimulation. Methods EPCs were treated with RSV and stimulated with TNF-α. A mononuclear cell (MNC) adhesion assay was used to assess the effects of RSV on TNF-α-induced MNC adhesion. Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression levels and nuclear factor κB (NF-κB) activation were assessed by immunoblotting. Results MNC adhesion to TNF-α-treated EPCs and VCAM-1/ICAM-1/E-selectin levels in EPCs were increased following TNF-α stimulation and decreased following RSV treatment. TNF-α enhanced NF-κB inhibitor α (IκB-α) phosphorylation in the cytosol as well as nuclear NF-κB p65 levels, both of which were decreased by RSV. Conclusions These findings provide new insights into RSV’s anti-inflammatory and anti-atherosclerotic effects. RSV’s mechanism of action might involve downregulation of VCAM-1, ICAM-1 and E-selectin by partial blockade of TNF-α-induced NF-κB activation and IκB-α phosphorylation in EPCs.

Neutralization of IL-18 attenuates lipopolysaccharide-induced myocardial dysfunction

2002 ◽  
Vol 283 (2) ◽  
pp. H650-H657 ◽  
Author(s):  
Christopher D. Raeburn ◽  
Charles A. Dinarello ◽  
Michael A. Zimmerman ◽  
Casey M. Calkins ◽  
Benjamin J. Pomerantz ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Developed Pressure ◽  
Factor Α ◽  
Cell Adhesion Molecule 1

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) have been implicated in cardiac dysfunction during endotoxemia. Because IL-18 is a proinflammatory cytokine known to mediate the production of TNF-α and IL-1β and to induce the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), we hypothesized that neutralization of IL-18 would attenuate lipopolysaccharide (LPS)-induced cardiac dysfunction. Mice (C57BL/6) were injected with LPS (0.5 mg/kg ip) or vehicle (normal saline), and left ventricular developed pressure (LVDP) was determined by the Langendorff technique. LVDP was depressed by 38% at 6 h after LPS. LPS-induced myocardial dysfunction was associated with increased myocardial levels of TNF-α and IL-1β as well as increased expression of ICAM-1/VCAM-1. Pretreatment with neutralizing anti-mouse IL-18 antibody attenuated LPS-induced myocardial dysfunction (by 92%) and was associated with reduced myocardial IL-1β production (65% reduction) and ICAM-1/VCAM-1 expression (50% and 35% reduction, respectively). However, myocardial TNF-α levels were not influenced by neutralization of IL-18. In conclusion, neutralization of IL-18 protects against LPS-induced myocardial dysfunction. IL-18 may mediate endotoxemic myocardial dysfunction through induction of and/or synergy with IL-1β, ICAM-1, and VCAM-1.

Παθοφυσιολογία της αντίδρασης του ενδοθηλίου μετά από αγγειοπλαστική νεφρικής αρτηρίας

2014 ◽  
Author(s):  
Κυριακή Ταβερναράκη
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Tnf Α ◽  
Factor Α ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor

Σκοπός:Για τη μελέτη του παθοφυσιολογικού μηχανισμού αντίδρασης του τοιχώματος της νεφρικής αρτηρίας που εκλύεται κατά την αγγειοπλαστική με τοποθέτηση stent πραγματοποιήθηκε ποσοτικός προσδιορισμός έξι διαφορετικών παραγόντων φλεγμονής -μεσολαβητών (κυτοκίνες) στον ορό αίματος ασθενών που υποβλήθηκαν σε αυτήν την μέθοδο. Απώτερος σκοπός της μελέτης, μέσω της αξιολόγησης των διαφορών στις συγκεντρώσεις των μεσολαβητών σε ασθενείς που εμφάνισαν ή όχι επαναστένωση του αγγείου, είναι η αναγνώριση καποιού παράγοντα φλεγμονής που θα αποτελέσει δείκτη πρόβλεψης της επαναστένωσης με στόχο την πρόληψη αυτής.Υλικό - Μέθοδος:Μελετήθηκαν είκοσι δύο ασθενείς (17 άνδρες, μέσος όρος ηλικίας 66 έτη), με στένωση στην έκφυση της νεφρικής αρτηρίας και μή καλώς ρυθμιζόμενη υπέρταση, οι οποίοι υποβλήθησαν σε αγγειοπλαστική νεφρικής αρτηρίας με τοποθέτηση stent. Στους ασθενείς αυτούς πραγματοποιήθηκαν αιμοληψίες σε τρεις διαφορετικούς χρόνους: αμέσως πριν την αγγειοπλαστική (baseline), 24 ώρες και 6 μήνες μετά την αγγειοπλαστική και μετρήθηκαν στον ορό τους οι εξής μεσολαβητές: (1) Παράγοντας Νέκρωσης Όγκου-α (Tumor necrosis factor-α, TNF-α), (2) Ιντερλευκίνη 6 (Interleukin-6, IL-6), (3) Πρωτεΐνη χημειοτακτική για τα μονοκύτταρα τύπου-1 (Monocyte Chemoattractant protein-1, MCP-1), (4) Διακυτταρικό μόριο προσκόλλησης-1 (Intercellular adhesion molecule-1, ICAM-1), (5) Μόριο προσκόλλησης αγγειακών κυττάρων-1 (Vascular cell Adhesion Molecule-1, VCAM-1) και (6) Παράγοντας RANTES (Regulated upon Activation Normal T-cell Expressed presumed Secreted). Στους έξι μήνες μετά την αγγειοπλαστική πραγματοποιήθηκε έχρωμο Doppler υπερηχογράφημα και καταγράφηκε η ανάπτυξη ή όχι επαναστένωσης εντός του stent. Επιπλέον, αξιολογήθηκαν οι διαφορές της συγκέντρωσης αυτών σε ασθενείς που εμφάνισαν επαναστένωση της νεφρικής αρτηρίας στους 6 μήνες μετά την αγειοπλαστική συγκριτικά με αυτούς που δεν εμφάνισαν επαναστένωση.Αποτελέσματα:Η συγκέντρωση της ΙL-6 αυξήθηκε σημαντικά 24 ώρες μετά την αγγειοπλαστική (8.3 pg/mL ± 1.24 vs 2.76 pg/mL ± 1.27 τιμές baseline), ενώ στους 6 μήνες μετά επέστρεψε στις προ την επέμβαση τιμές (2.6 pg/mL ± 1.77) (Ρ<.0001). Δεν σημειώθηκαν στατιστικά σημαντικές διαφορές στις συγκεντρώσεις των υπολοίπων μεσολαβητών σε κανέναν από τους τρεις χρόνους. Επίσης, βρέθηκε πως η συγκέντρωση της ΙL-6 τόσο πρίν την αγγειοπλαστική όσο και 6 μήνες μετά την αγγειοπλαστική ήταν σημαντικά υψηλότερη στους ασθενείς που ανάπτυξαν επαναστένωση (8.13 pg/mL ± 4 vs 0.75 pg/mL ± 0.47 [P,.005] και 9.55 pg/ml ± 6.5 vs 0.42 pg/ml ± 0.35 [p<.02] αντίστοιχα).Συμπέρασμα:Με βάση τα αποτελέσματα προτείνουμε πως η αγγειοπλαστική της νεφρικής αρτηρίας με τοποθέτηση stent προκαλεί μια φλεγμονώδη αντίδραση στο τοίχωμα της αρτηρίας, όπως αυτή εκφράζεται με την υψηλή συγκέντρωση ΙL-6 στο αίμα 24 ώρες μετά την επέμβαση. Όσον αφορά στην ανάπτυξη ή όχι επαναστένωσης του αγγείου προτείνουμε πως η ΙL-6 μπορεί να να αναγνωρίσει τους ασθενείς υψηλού κινδύνου και κατ’ επέκταση να αποτελέσει έναν δείκτη πρόβλεψης της επαναστένωσης.

scholarly journals Inflammatory and endothelial dysfunction markers and proteinuria in persons with type 1 diabetes mellitus

2010 ◽  
Vol 162 (6) ◽  
pp. 1101-1105 ◽  
Author(s):  
Karine Sahakyan ◽  
Barbara E K Klein ◽  
Kristine E Lee ◽  
Michael Y Tsai ◽  
Ronald Klein
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Endothelial Dysfunction ◽  
Type 1 Diabetes Mellitus ◽  
Adhesion Molecule ◽  
High Sensitivity ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α

ObjectiveWe examined the relationship of inflammatory and endothelial dysfunction markers with the prevalence and incidence of gross proteinuria (GP) in persons with type 1 diabetes mellitus.DesignA longitudinal population-based cohort of persons with type 1 diabetes mellitus was followed from 1990–1992 through 2005–2007.MethodsPrevalence and 15-year cumulative incidence of GP were defined as outcome variables. Serum high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1, and serum total homocysteine were measured. Multivariate logistic and discrete linear logistic regression modeling was used for data analysis.ResultsAfter controlling for duration of diabetes and other confounding factors, TNF-α (odds ratio (OR) 3.64; 95% confidence interval (CI) 2.33, 5.70), IL-6 (OR 1.41; 95% CI 1.06, 1.88), VCAM-1 (OR 13.35; 95% CI 5.39, 33.07), and homocysteine (OR 2.98; 95% CI 1.73, 5.16) were associated with prevalent proteinuria. Only hsCRP (OR 1.47; 95% CI 1.02, 2.11) was associated with incident proteinuria.ConclusionsThese findings suggest a role of inflammation and endothelial dysfunction as markers and contributors of the development of diabetic nephropathy in persons with type 1 diabetes mellitus.

scholarly journals Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium

1998 ◽  
Vol 331 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Toshiyuki ARAI ◽  
Susan A. KELLY ◽  
Matthew L. BRENGMAN ◽  
Manabu TAKANO ◽  
Elise H. SMITH ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Adhesion Molecule ◽  
Tumour Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Tumour Necrosis Factor Α ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor α (TNF-α) in vitro. TNF-α upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-α was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-α. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-α to induce ICAM-1 expression in endothelium in vitro.

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

2018 ◽  
Vol 74 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Joanna J. Samulak ◽  
Angelika K. Sawicka ◽  
Dace Hartmane ◽  
Solveiga Grinberga ◽  
Osvalds Pugovics ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Adhesion Molecule ◽  
Serum Proteins ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Intercellular Adhesion Molecule ◽  
Carnitine Supplementation ◽  
Intercellular Adhesion Molecule 1 ◽  
Factor Α

Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that ­although oral L-carnitine supplementation significantly ­increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

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