scholarly journals Protective Effect of Proanthocyanidin against Diabetic Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Takako Yokozawa ◽  
Eun Ju Cho ◽  
Chan Hum Park ◽  
Ji Hyun Kim
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Serum Glucose ◽  
Ros Generation ◽  
Diabetic Mice ◽  
Polymeric Form ◽  
Inflammatory Reactions ◽  
Oligomeric Form ◽  
Type 2 Diabetic

We investigated the antidiabetic potential of proanthocyanidin and its oligomeric form in STZ-induced diabetic model rats anddb/dbtype 2 diabetic mice. Proanthocyanidin ameliorated the diabetic condition by significant decreases of serum glucose, glycosylated protein, and serum urea nitrogen as well as decreases of urinary protein and renal-AGE in STZ-induced diabetic rats and decrease of serum glucose as well as significant decrease of glycosylated protein indb/dbtype 2 diabetic mice. The suppression of ROS generation and elevation of the GSH/GSSG ratio were also observed in the groups administered proanthocyanidin. Moreover, proanthocyanidin, especially its oligomeric form, affected the inflammatory process with the regulation of related protein expression, iNOS, COX-2 and upstream regulators, NF-κB, and the IκB-α. In addition, it had a marked effect on hyperlipidemia through lowering significant levels of triglycerides, total cholesterol, and NEFA. Moreover, expressions in the liver of SREBP-1 and SREBP-2 were downregulated by the administration of proanthocyanidins. The protective effect against hyperglycemia and hyperlipidemia in type 1 and 2 diabetic models was significantly strong in the groups administered the oligomeric rather than polymeric form. This suggests that oligomers act as a regulator in inflammatory reactions caused by oxidative stress in diabetes.

Renoprotective Effects of Metformin and Its Relationship with Oxidative Stress in Type 2 Diabetic Mice

2021 ◽  
Author(s):  
Wen Wenjie ◽  
Zhang Qilun ◽  
Bi shuangjie ◽  
Xue Jingfan ◽  
Wu Xiaoying ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Renal Tissue ◽  
Retinol Binding Protein ◽  
Control Group ◽  
Membrane Thickness ◽  
Diabetic Mice ◽  
Basement Membrane Thickness ◽  
Type 2 Diabetic

Abstract Background: Oxidative stress has previously been shown to play critical roles in the development of diabetes and its complications. The purpose of this research was to observe the reno-protective effect of metformin and its effect on oxidative stress in type 2 diabetic mice renal tissue.Methods: Type 2 diabetes mellitus mice model was established by High-fat feed combined with small-dose STZ and randomly divided into diabetes model group, Metformin [MET, 250mg/(kg.d)] group, Glibenclamide (GLIB) [GLIB, 2.5mg/(kg.d)] group, and normal control group (NC). After 8 weeks of intervention, blood and urine samples were collected for detection of FBG, HbA1c, urine albumin (Alb), retinol-binding protein (RBP), podocalyxin (PCX), 8-OHdG, 8-iso-PG, and creatinine (Cr). Renal tissue specimens were preserved for observing renal glomerular basement membrane thickness (GBMT) and foot process fusion rate (FPFR) under electron microscopy.Results: Compared with the NC group, FBG, HbA1c, urinary Alb/Cr (UACR), RBP/Cr (URCR), PCX/Cr (UPCR), 8-OHdG /Cr (UOHCR), and 8-iso-PG /Cr (UISOCR) significantly increased in the T2DM group (P <0.05). Compared with the T2DM group, FBG, HbA1c, UACR, URCR, UPCR, UOHCR, and UISOCR were significantly reduced in the GLIB group and MET group (P <0.05). Compared to the GLIB group, UACR, URCR, UPCR, UOHCR, and UISOCR decreased in the MET group (P <0.05), but FBG and HbA1c were not differenced statistically between the two groups. GBMT and FPFR increased in the T2DM group (P <0.05), which were reduced in the MET group and lighter than those in the GLIB group (P <0.05).Conclusion: Metformin intervention can play a reno-protective effect in type 2 diabetic mice, which may be related to its effect in inhibiting enhanced oxidative stress in vivo.

scholarly journals Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 557
Author(s):  
Stephanie D. Burr ◽  
James A. Stewart
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Hydrogen Peroxide ◽  
Cardiac Fibroblasts ◽  
The Body ◽  
Signaling Cascade ◽  
Diabetic Mice ◽  
Pkc Ζ ◽  
Type 2 Diabetic

Cardiovascular disease, specifically heart failure, is a common complication for individuals with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by “active” cardiac fibroblasts (i.e., myofibroblasts) remodeling the extracellular matrix (ECM). Differentiation of fibroblasts to myofibroblasts has been demonstrated to be an outcome of AGE/RAGE signaling. Hyperglycemia causes advanced glycated end products (AGEs) to accumulate within the body, and this process is greatly accelerated under chronic diabetic conditions. AGEs can bind and activate their receptor (RAGE) to trigger multiple downstream outcomes, such as altering ECM remodeling, inflammation, and oxidative stress. Previously, our lab has identified a small GTPase, Rap1a, that possibly overlaps the AGE/RAGE signaling cascade to affect the downstream outcomes. Rap1a acts as a molecular switch connecting extracellular signals to intracellular responses. Therefore, we hypothesized that Rap1a crosses the AGE/RAGE cascade to alter the expression of AGE/RAGE associated signaling proteins in cardiac fibroblasts in type 2 diabetic mice. To delineate this cascade, we used genetically different cardiac fibroblasts from non-diabetic, diabetic, non-diabetic RAGE knockout, diabetic RAGE knockout, and Rap1a knockout mice and treated them with pharmacological modifiers (exogenous AGEs, EPAC, Rap1a siRNA, and pseudosubstrate PKC-ζ). We examined changes in expression of proteins implicated as markers for myofibroblasts (α-SMA) and inflammation/oxidative stress (NF-κB and SOD-1). In addition, oxidative stress was also assessed by measuring hydrogen peroxide concentration. Our results indicated that Rap1a connects to the AGE/RAGE cascade to promote and maintain α-SMA expression in cardiac fibroblasts. Moreover, Rap1a, in conjunction with activation of the AGE/RAGE cascade, increased NF-κB expression as well as hydrogen peroxide concentration, indicating a possible oxidative stress response. Additionally, knocking down Rap1a expression resulted in an increase in SOD-1 expression suggesting that Rap1a can affect oxidative stress markers independently of the AGE/RAGE signaling cascade. These results demonstrated that Rap1a contributes to the myofibroblast population within the heart via AGE/RAGE signaling as well as promotes possible oxidative stress. This study offers a new potential therapeutic target that could possibly reduce the risk for developing diabetic cardiovascular complications attributed to AGE/RAGE signaling.

Moringa oleifera from Cambodia Ameliorates Oxidative Stress, Hyperglycemia, and Kidney Dysfunction in Type 2 Diabetic Mice

2017 ◽  
Vol 20 (5) ◽  
pp. 502-510 ◽  
Author(s):  
Yujiao Tang ◽  
Eun-Ju Choi ◽  
Weon Cheol Han ◽  
Mirae Oh ◽  
Jin Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Moringa Oleifera ◽  
Diabetic Mice ◽  
Kidney Dysfunction ◽  
Stress Hyperglycemia ◽  
Type 2 Diabetic

scholarly journals Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes

2012 ◽  
Vol 216 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Lucy M Hinder ◽  
Anuradha Vivekanandan-Giri ◽  
Lisa L McLean ◽  
Subramaniam Pennathur ◽  
Eva L Feldman
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Sural Nerve ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted liquid chromatography–tandem mass spectrometry (LC/MS/MS) to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve, and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Leprdb;db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, and lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve, and DRG from diabetic mice. Utilizing LC/electrospray ionization/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids) indb/dbtissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerves to rely on truncated TCA cycle metabolism in the type 2 diabetes environment.

scholarly journals The Synergistic Effect of Valsartan and LAF237 [(S)-1-[(3-Hydroxy-1-Adamantyl)Ammo]acetyl-2-Cyanopyrrolidine] on Vascular Oxidative Stress and Inflammation in Type 2 Diabetic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Min Shen ◽  
Dongdong Sun ◽  
Weijie Li ◽  
Bing Liu ◽  
Shenxu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Combination Treatment ◽  
Fold Change ◽  
Diabetic Mice ◽  
Dpp Iv ◽  
Vascular Oxidative Stress ◽  
To Receive ◽  
Type 2 Diabetic

Aim. To investigate the combination effects and mechanisms of valsartan (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on prevention against oxidative stress and inflammation injury in db/db mice aorta.Methods. Db/db mice (n=40) were randomized to receive valsartan, LAF237, valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in diabetic mice aorta were examined.Results. Valsartan or LAF237 pretreatment significantly increased plasma GLP-1 expression, reduced apoptosis of endothelial cells isolated from diabetic mice aorta. The expression of NAD(P)H oxidase subunits also significantly decreased resulting in decreased superoxide production and ICAM-1 (fold change: valsartan : 7.5 ± 0.7,P<0.05; LAF237: 10.2 ± 1.7,P<0.05), VCAM-1 (fold change: valsartan : 5.2 ± 1.2,P<0.05; LAF237: 4.8 ± 0.6,P<0.05), and MCP-1 (fold change: valsartan: 3.2 ± 0.6, LAF237: 4.7 ± 0.8;P<0.05) expression. Moreover, the combination treatment with valsartan and LAF237 resulted in a more significant increase of GLP-1 expression. The decrease of the vascular oxidative stress and inflammation reaction was also higher than monotherapy with valsartan or LAF237.Conclusion. These data indicated that combination treatment with LAF237 and valsartan acts in a synergistic manner on vascular oxidative stress and inflammation in type 2 diabetic mice.

scholarly journals Role of Advanced Glycation Products with Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic mice

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Jun Su ◽  
Pamela Lucchesi ◽  
Yasuhiro Suzuki ◽  
Bashir M Rezk ◽  
Desiree I Palen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Mice ◽  
Resistance Artery ◽  
Advanced Glycation ◽  
Type 2 Diabetic
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