Resveratrol Protects against Oxidative Stress‐Induced Endothelial Dysfunction in Type II Diabetes

2008 ◽  
Vol 22 (S2) ◽  
pp. 42-42
Author(s):  
Hanrui Zhang ◽  
Minga Sellers ◽  
Zoltan Ungvari ◽  
Cuihua Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Type Ii Diabetes ◽  
Type Ii

Abstract 243: Roles of TNF alpha and MCP-1 in Type II Diabetes-induced Endothelial Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jiyeon Yang ◽  
Abbott C Louise ◽  
Cuihua Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Type Ii Diabetes ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Heart Tissue ◽  
Type Ii ◽  
Necrosis Factor Alpha ◽  
Double Labeling ◽  
Monocyte Chemoattractant Protein 1

Tumor necrosis factor alpha (TNF) is reported to underlie a component of vascular inflammation and ensuing endothelial dysfunction in diabetes, but the role of inflammatory cells in these events is unknown. Because TNF reportedly induces monocyte chemoattractant protein-1 (MCP-1) expression, we hypothesized that the interaction between TNF and MCP-1 contributes to the evolution of vascular inflammation in diabetes. To test this hypothesis, expression of TNF and MCP-1, and formation of nitrotyrosine (N-Tyr, an indicator of peroxynitrite production) were determined in isolated coronary arterioles (50–100um) from genetically modified mice with Type II diabetes (Lepr db ) and the lean control heterozygotes (m Lepr db ). Protein and mRNA expression of TNF, protein expression of MCP-1, and presence of N-Tyr were significantly increased in arterioles from Lepr db mice compared to those from m Lepr db . Immunofluorescence double labeling revealed the prominent localization of MCP-1 to endothelium (Von Willebrand factor) of arterioles and venules. MCP-1 also co-localized with macrophages (CD68) in the heart tissue. To determine if MCP-1 may be key to the vascular inflammation and ensuing endothelial dysfunction, we administered anti-MCP-1 (10 μg/day, 3 days, i.p., n=4; to block MCP-1 signaling) in the mice and then determined endothelial dilation in isolated, cannulated pressurized (60 cmH2O) arterioles. Anti-MCP-1 restored dilation to acetylcholine in Lepr db mice by 35±2% (P<0.05 vs Lepr db mice without treatment, 9.8±4%) but did not affect dilation in m Lepr db mice. To establish interactions between TNF and MCP-1, we administered anti-TNF (72hr treatment; 0.625mg/kg, i.p.) to block TNF signaling and determined effects on MCP-1 and oxidative stress. After anti-TNF administration, expression of MCP-1 was decreased and numbers of MCP-1 positive cells were markedly reduced in Lepr db mice. Moreover, anti-TNF prevented the formation of N-Tyr in Lepr db mice. These findings demonstrate that the endothelial dysfunction occurring in type II diabetes is the result of the effects of the inflammatory cytokine TNF and TNF related signaling, including the expression of MCP-1, which also furthers the oxidative stress.

Abstract 890: Feed-forward Signaling of TNF alpha and NFkappa B Produces Endothelial Dysfunction in Coronary Arterioles In Type Ii Diabetic Mice.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jiyeon Yang ◽  
Xiangbin Xu ◽  
Glen A Laine ◽  
Cuihua Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Type Ii ◽  
Diabetic Mice ◽  
Necrosis Factor Alpha ◽  
Paramagnetic Resonance ◽  
Feed Forward ◽  
Coronary Arterioles

Nuclear factor-κB (NFκB) signaling reportedly increases tumor necrosis factor-alpha (TNF expression), and the oxidative stress induced by TNF may then lead to further increase NFκB expression, i.e., a feed-forward interaction. Accordingly, we hypothesized that this feed-forward interaction between TNF and NFκB may amplify one another toward the evolution of vascular disease in diabetes. To test this hypothesis, we assessed the role of NFκB in endothelial dysfunction in Lepr db mice by evaluation of endothelial function of isolated coronary resistance vessels of m Lepr db (heterozygote, normal) and Lepr db (homozygote, diabetic) mice. Coronary arterioles (40 –100 μm) were isolated and pressurized (60 cmH2O) without flow. Although dilation of vessels to the endothelium-independent vasodilator, sodium nitroprusside (SNP) was not different between Lepr db and m Lepr db mice (n = 6), dilation to the endothelium-dependent agonist, acetycholine (ACh) was reduced (n = 5, P < 0.05). Electron Paramagnetic Resonance (EPR) results show that superoxide production was reduced by NFκB antagonist (MG-132), or anti-TNF in Lepr db mice suggesting that NFκB and TNF were contributing to elevated oxidative stress. MG-132 (1 μM, n = 4) antagonized the inhibitory effect of Lepr db mice on ACh-induced dilation vs. Lepr db without treatment, but did not affect dilation in m Lepr db mice. To better understand the basis for enhanced contributions of TNF and NFκB in diabetes, we used Western analysis to assess expression of major proteins involved in TNF-mediated signaling. Previous studies have provided compelling evidence that IKK beta plays an essential role in NFκB activation in response to TNF, whereas IKK alpha appears to play a lesser role; therefore, we examined the expression levels of IKK alpha and IKK beta mRNA and protein in Lepr db null for TNF. The protein concentration and mRNA expression level of IKK alpha were increased in Lepr db mice null for TNF (db TNF- /db TNF- ) mice. One intriguing finding of this study is that the roles of IKK alpha and IKK beta appear reversed in the inflammatory response in diabetic Lepr db mice. Furthermore, our results indicate that NFκB and TNF signaling interact to amplify the oxidative stress and induce endothelial dysfunction in type II diabetes.

scholarly journals Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus

Diabetologia ◽  
2002 ◽  
Vol 45 (3) ◽  
pp. 420-426 ◽  
Author(s):  
G. F. Watts ◽  
D. A. Playford ◽  
K. D. Croft ◽  
N. C. Ward ◽  
T. A. Mori ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Brachial Artery ◽  
Coenzyme Q10 ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii

PONI and its association with oxidative stress in type I and type II diabetes mellitus

2011 ◽  
Vol 5 (3) ◽  
pp. 126-129 ◽  
Author(s):  
Sandhya Pillai Nair ◽  
N.C. Shah ◽  
Anand Taggarsi ◽  
Uma Nayak
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Type I ◽  
Type Ii

Changes in plasma lipids and markers of oxidative stress in normal pregnancy and pregnancies complicated by diabetes

2004 ◽  
Vol 106 (1) ◽  
pp. 93-98 ◽  
Author(s):  
V. TOESCU ◽  
S. L. NUTTALL ◽  
U. MARTIN ◽  
P. NIGHTINGALE ◽  
M. J. KENDALL ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pregnant Women ◽  
Total Cholesterol ◽  
Type Ii Diabetes ◽  
Plasma Lipids ◽  
Lipid Hydroperoxides ◽  
Type I ◽  
Type Ii ◽  
Markers Of Oxidative Stress ◽  
Normal Women

The purpose of the present study was to determine changes in plasma lipids and markers of oxidative stress longitudinally in pregnancy complicated by diabetes compared with non-diabetic pregnancy. This was carried out by following a group of normal pregnant women (n=17) and groups of pregnant women with Type I diabetes (n=19), Type II diabetes (n=12) and gestational diabetes mellitus (n=12) throughout pregnancy, with sampling carried out at the end of each trimester. Serum total cholesterol and triacylglycerols (triglycerides) were determined using standard colorimetric techniques and low-density lipoprotein (LDL) subfraction profile by disc PAGE. Total antioxidant capacity (TAC) was determined by enhanced chemiluminescence and lipid hydroperoxides by the ferrous oxidation of Xylenol Orange method. Total cholesterol and triacylglycerols increased significantly throughout pregnancy in all groups, but there were no significant differences between normal and diabetic women with respect to either. The LDL score was significantly higher (P<0.001) in diabetic women compared with normal women at each point throughout pregnancy, although there were no significant differences between the diabetic groups. There was evidence of greater oxidative stress in diabetic compared with normal women throughout. Corrected TAC was significantly lower (P<0.001) in all diabetic women throughout pregnancy. In addition, lipid hydroperoxides were higher in all diabetic compared with normal women, particularly so in those with Type II diabetes (P<0.05). These changes may have important implications for diabetic women during pregnancy, as an elevated risk of pre-eclampsia is thought to reflect an oxidative stress-related mechanism. In addition, these changes may have important implications for the development of atherosclerosis and the long-term cardiovascular health of women with diabetes.

Glycoxidation, and protein and DNA oxidation in patients with diabetes mellitus

1998 ◽  
Vol 95 (3) ◽  
pp. 331-337 ◽  
Author(s):  
K. KRAPFENBAUER ◽  
R. BIRNBACHER ◽  
H. VIERHAPPER ◽  
K. HERKNER ◽  
D. KAMPEL ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Hydroxyl Radical ◽  
Protein Oxidation ◽  
Type Ii Diabetes ◽  
Dna Oxidation ◽  
Type I ◽  
Type Ii ◽  
Patients With Diabetes ◽  
Radical Attack

1.The role of oxidative stress in the pathogenesis of the diabetic state is being investigated extensively. Although oxidative stress has been reported in terms of glycoxidation, protein oxidation and DNA oxidation in diabetes mellitus, oxidation parameters have not been determined in parallel on the same study population. 2.We studied 24 patients with diabetes mellitus (14 patients with Type I diabetes with a mean age of 62.3±6.3 years and 10 patients with Type II diabetes aged 67.3±5.9 years) and compared them with age-matched non-diabetic controls. Urinary o-tyrosine, 8-hydroxy-2′-deoxyguanosine and pentosidine measurements by HPLC were made on two occasions (t1 and t2). 3.A clear statistical difference was found between diabetic patients and controls at t1 or t2 for 8-hydroxy-2′-deoxyguanosine and pentosidine, but not for o-tyrosine. No significant correlations were found between clinical and other laboratory parameters except high-density lipoprotein and uric acid. We revealed significantly increased glycoxidation and DNA oxidation in patients with Type I and Type II diabetes, but protein oxidation was not different from controls. 4.The finding of increased glycoxidation reflects increased oxidation of the carbohydrate moiety, whereas the increased levels of oxidized DNA may also be interpreted as due to increased DNA repair. The increased 8-hydroxy-2′-deoxyguanosine does not indicate the generation of an individual active oxygen species, but DNA could have been oxidized simply by alkenals from lipid peroxidation, as e.g. malondialdehyde. As no difference in protein oxidation (i.e. o-tyrosine) between diabetics and controls could be revealed, the oxidation of DNA by hydroxyl radical attack is unlikely, as o-tyrosine was proposed as a marker for hydroxyl radical attack. Therefore, the message is that increased glycoxidation can be confirmed, protein oxidation does not appear to take place and increased DNA oxidation is still not proven, as increased 8-hydroxy-2′-deoxyguanosine may simply reflect repair.

scholarly journals NF-κB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes

2009 ◽  
Vol 85 (3) ◽  
pp. 473-483 ◽  
Author(s):  
Nithya Mariappan ◽  
Carrie M. Elks ◽  
Srinivas Sriramula ◽  
Anuradha Guggilam ◽  
Zhizhen Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Type Ii Diabetes ◽  
Type Ii
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