scholarly journals The Antioxidant 3H-1,2-Dithiole-3-Thione Potentiates Advanced Glycation End-Product-Induced Oxidative Stress in SH-SY5Y Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Robert Pazdro ◽  
John R. Burgess
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Antioxidant Defenses ◽  
Chemical Induction ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
Ros Formation ◽  
Endogenous Antioxidant ◽  
Neurite Degeneration

Oxidative stress is implicated as a major factor in the development of diabetes complications and is caused in part by advanced glycation end products (AGEs). AGEs ligate to the receptor for AGEs (RAGE), promoting protein kinase C (PKC)-dependent activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide radical generation. While scavenging antioxidants are protective against AGEs, it is unknown if induction of endogenous antioxidant defenses has the same effect. In this study, we confirmed that the compound 3H-1,2-dithiole-3-thione (D3T) increases reduced-state glutathione (GSH) concentrations and NADPH:quinone oxidoreductase 1 (NQO1) activity in SH-SY5Y cells and provides protection against H2O2. Surprisingly, D3T potentiated oxidative damage caused by AGEs. In comparison to vehicle controls, D3T caused greater AGE-induced cytotoxicity and depletion of intracellular GSH levels while offering no protection against neurite degeneration or protein carbonylation. D3T potentiated AGE-induced reactive oxygen species (ROS) formation, an effect abrogated by inhibitors of PKC and NADPH oxidase. This study suggests that chemical induction of endogenous antioxidant defenses requires further examination in models of diabetes.

scholarly journals Sitagliptin attenuates arterial calcification by downregulating oxidative stress-induced receptor for advanced glycation end products in LDLR knockout mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chih-Pei Lin ◽  
Po-Hsun Huang ◽  
Chi-Yu Chen ◽  
Meng-Yu Wu ◽  
Jia-Shiong Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Advanced Glycation End Products ◽  
Calcium Deposition ◽  
Arterial Calcification ◽  
Advanced Glycation ◽  
Tnf Α ◽  
Glycation End Products ◽  
End Products ◽  
Rage Expression

AbstractDiabetes is a complex disease characterized by hyperglycemia, dyslipidemia, and insulin resistance. Plasma advanced glycation end products (AGEs) activated the receptor for advanced glycation end products (RAGE) and the activation of RAGE is implicated to be the pathogenesis of type 2 diabetic mellitus (T2DM) patient vascular complications. Sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, is a new oral hypoglycemic agent for the treatment of T2DM. However, the beneficial effects on vascular calcification remain unclear. In this study, we used a high-fat diet (HFD)-fed low-density lipoprotein receptor deficiency (LDLR−/−) mice model to investigate the potential effects of sitagliptin on HFD-induced arterial calcification. Mice were randomly divided into 3 groups: (1) normal diet group, (2) HFD group and (3) HFD + sitagliptin group. After 24 weeks treatment, we collected the blood for chemistry parameters and DPP4 activity measurement, and harvested the aorta to evaluate calcification using immunohistochemistry and calcium content. To determine the effects of sitagliptin, tumor necrosis factor (TNF)-α combined with S100A12 was used to induce oxidative stress, activation of nicotinamide adenine dinucleotide phosphate (NADPH), up-regulation of bone markers and RAGE expression, and cell calcium deposition on human aortic smooth muscle cells (HASMCs). We found that sitagliptin effectively blunted the HFD-induced artery calcification and significantly lowered the levels of fasting serum glucose, triglyceride (TG), nitrotyrosine and TNF-α, decreased the calcium deposits, and reduced arterial calcification. In an in-vitro study, both S100A12 and TNF-α stimulated RAGE expression and cellular calcium deposits in HASMCs. The potency of S100A12 on HASMCs was amplified by the presence of TNF-α. Sitagliptin and Apocynin (APO), an NADPH oxidase inhibitor, inhibited the TNF-α + S100A12-induced NADPH oxidase and nuclear factor (NF)-κB activation, cellular oxidative stress, RAGE expression, osteo transcription factors expression and calcium deposition. In addition, treatment with sitagliptin, knockdown of RAGE or TNF-α receptor blunted the TNF-α + S100A12-induced RAGE expression. Our findings suggest that sitagliptin may suppress the initiation and progression of arterial calcification by inhibiting the activation of NADPH oxidase and NF-κB, followed by decreasing the expression of RAGE.

scholarly journals Plasmatic Soluble Receptor for Advanced Glycation End Products as a New Oxidative Stress Biomarker in Patients with Prosthetic-Joint-Associated Infections?

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Luca Massaccesi ◽  
Barbara Bonomelli ◽  
Monica Gioia Marazzi ◽  
Lorenzo Drago ◽  
Massimiliano Marco Corsi Romanelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Early Diagnosis ◽  
Advanced Glycation End Products ◽  
Antioxidant Defenses ◽  
Thiobarbituric Acid Reactive Substance ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Prosthetic Joint ◽  
Glycation End Products ◽  
End Products

Prosthetic joint infection (PJI) is the most common cause of failure of total joint arthroplasty, but a gold standard for PJI diagnosis is still lacking. Advanced glycation end products (AGEs) are proinflammatory molecules inducing intracellular oxidative stress (OS) after binding to their cell membrane receptors (RAGE). The aim of this study was to evaluate plasmatic soluble receptor for advanced glycation end products (sRAGE), as a new OS and infection marker correlating sRAGE to the level of OS and antioxidant defenses, in PJI, in order to explore the possible application of this new biomarker in the early diagnosis of PJI. Plasmatic sRAGE levels (by ELISA assay), plasma antioxidant total defenses (by lag time method), plasma reactive oxygen species (ROS), and thiobarbituric acid reactive substance (TBARS) levels (by colorimetric assay) were evaluated in 11 PJI patients and in 30 matched controls. ROS and TBARS were significantly higher (p<0.001) while plasma total antioxidant capacity and sRAGE were significantly lower (p<0.01) in patients with PJI compared to controls. Our results confirm the OS in PJI and show a strong negative correlation between the level of sRAGE and oxidative status, suggesting the plasmatic sRAGE as a potential marker for improving PJI early diagnosis.

scholarly journals Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Attenuates Arterial Calcification By Downregulating Oxidative Stress-Induced Receptor for Advanced Glycation End Products in Low-Density Lipoprotein Receptor Knockout Mice

2021 ◽  
Author(s):  
Chih Pei Lin ◽  
Po-Hsun Huang ◽  
Chi-Yu Chen ◽  
Jia-Shiong Chen ◽  
Jaw-Wen Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Advanced Glycation End Products ◽  
Calcium Deposition ◽  
Advanced Glycation ◽  
Dipeptidyl Peptidase 4 ◽  
Tnf Α ◽  
Glycation End Products ◽  
End Products ◽  
Rage Expression

Abstract Background: Plasma advanced glycation end products (AGEs) activates the receptor for advanced glycation end products (RAGE) and the activation of RAGE is implicated to be the pathogenesis of type 2 diabetic mellitus patient vascular complications. Attenuating the activation of RAGE may exert a protective effect against the development of cardiovascular disease. Dipeptidyl peptidase-4 (DPP4) inhibitors are a new class of oral hypoglycemic agents for the treatment of type 2 diabetes mellitus. Whether sitagliptin, a DPP-4 inhibitor, has a beneficial effect on vascular calcification remains undetermined. Methods: In the present study, we fed low-density lipoprotein receptor knockout (LDLR-/-) mice a high fat diet to induce diabetic mellitus and studied the effect of orally administered sitagliptin on the high fat diet fed LDLR-/- mice aorta medial calcification, RAGE expression, oxidative stress, aorta calcium content. Tumor necrosis factor (TNF)-α combined with S100A12 was used to induce HASMC oxidative stress, activation of NADPH, up-regulation of the bone markers and RAGE expression, and cell calcium deposition. Effect of sitagliptin, siRNA for RAGE and apocynin on blunting TNF-α and S100A12 induced HASMC oxidative stress, calcification and NADPH activation were also investigated. Results: Sitagliptin attenuated the HFD-induced LDLR-/- mice hyperlipidemia, hyperglycemia, increase in serum TNF-α, aorta calcium deposition and the expression of RAGE in the medial layer of the aorta. TNF-α combined with S100A12 stimulated HASMC RAGE expression, calcium deposition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activation, and up-regulation of bone marker (bone morphogenetic protein-2, Msh homeobox 2, and runt‑related transcription factor 2) expression. Sitagliptin and apocynin (APO), an NADPH oxidase inhibitor, suppressed the TNF-α+S100A12 treatment effects on the activation of NADPH oxidase and Nuclear factor (NF)-κB and the resultant oxidative stress, up-regulation of RAGE and bone markers expression and calcium deposition. Our findings suggest that sitagliptin imparts its protective effect by suppressing NADPH oxidase and NF-κB activation to blunt the up-regulation of RAGE expression.Conclusion: Our findings suggest that sitagliptin may suppress the initiation and progression of artery calcification by inhibiting the activation of NADPH oxidase and NF-κB and the resultant up-regulation of expression of RAGE.

scholarly journals NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sunil Joshi ◽  
Ammon B. Peck ◽  
Saeed R. Khan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tissue Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Renal Tissue ◽  
Oxygen Species ◽  
Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

scholarly journals Advanced Glycation End Products and Oxidative Stress in a Hyperglycaemic Environment

2021 ◽  
Author(s):  
Akio Nakamura ◽  
Ritsuko Kawahrada
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Advanced Glycation End Products ◽  
Reactive Oxygen ◽  
Protein Glycation ◽  
Oxygen Species ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

Protein glycation is the random, nonenzymatic reaction of sugar and protein induced by diabetes and ageing; this process is quite different from glycosylation mediated by the enzymatic reactions catalysed by glycosyltransferases. Schiff bases form advanced glycation end products (AGEs) via intermediates, such as Amadori compounds. Although these AGEs form various molecular species, only a few of their structures have been determined. AGEs bind to different AGE receptors on the cell membrane and transmit signals to the cell. Signal transduction via the receptor of AGEs produces reactive oxygen species in cells, and oxidative stress is responsible for the onset of diabetic complications. This chapter introduces the molecular mechanisms of disease onset due to oxidative stress, including reactive oxygen species, caused by AGEs generated by protein glycation in a hyperglycaemic environment.

Citrus Fruit Extracts Reduce Advanced Glycation End Products (AGEs)- and H2O2-Induced Oxidative Stress in Human Adipocytes

2010 ◽  
Vol 58 (20) ◽  
pp. 11119-11129 ◽  
Author(s):  
Deena Ramful ◽  
Evelyne Tarnus ◽  
Philippe Rondeau ◽  
Christine Robert Da Silva ◽  
Theeshan Bahorun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Advanced Glycation End Products ◽  
Citrus Fruit ◽  
Human Adipocytes ◽  
Advanced Glycation ◽  
Fruit Extracts ◽  
Glycation End Products ◽  
End Products
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