Total Plasma Antioxidant Capacity Predicts Thrombosis-Prone Status in NIDDM Patients

Ceriello, Antonio; Bortolotti, Nadia; Pirisi, Mario; Crescentini, Adriana; Tonutti, Laura; Motz, Enrico; Russo, Assunta; Giacomello, Roberta; Stel, Giuliana; Taboga, C.

doi:10.2337/diacare.20.10.1589

Cited by 56 publications

(25 citation statements)

References 41 publications

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“…Nevertheless, it has been shown that oxidative stress is markedly increased in diabetes (Giugliano et al 1996). Several reports have described elevations in specific oxidative stress markers (Kennedy and Lyons 1997;Rosen et al 1998), together with reduced total antioxidant defense and depletions in individual antioxidants in diabetes (Ceriello et al 1997a(Ceriello et al , 1997b. The cause of free radical production is not yet fully resolved.…”

Section: Discussionmentioning

confidence: 98%

Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients

et al. 2002

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Heme oxygenase is a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide. Induction of heme oxygenase-1 is implicated in the antioxidant defense mechanism and can modulate vascular function. To test the association of microsatellite polymorphism in the promoter region of human HO-1 gene with the risk of coronary artery disease (CAD) in type 2 diabetic patients, we examined the allele frequencies of (GT) (n) repeats in HO-1 gene in 474 patients with CAD and in 322 controls. A transient-transfection assay with HO-1 promoter/luciferase fusion constructs carrying various lengths of (GT) (n) repeats was performed to explore the regulatory effect of (GT) (n) repeats on HO-1 gene expression in cultured rat aortic smooth muscle cells. Serum thiobarbituric acid-reactive substances (TBARs), a measure of lipid peroxidation, was significantly higher in subjects carrying the L/L genotype (> or =32 repeats). Among type 2 diabetic subjects, the frequencies of the L alleles and proportion of genotypes with L alleles were significantly higher in those with CAD than in those without CAD. The adjusted odds ratio for CAD in type 2 diabetic patients with L alleles was 4.7 (95% confidence interval, 1.9-12.0, P=0.001). Transfection experiments in aortic smooth muscle cells revealed that HO-1 promoter/luciferase fusion constructs containing longer (GT) (n) repeats exhibited lower transcriptional activity. These results imply that the length polymorphism in the HO-1 gene promoter modulate the transcription of the gene in vascular cells. Type 2 diabetics carrying longer (GT) (n) repeats might have higher oxidative stress and increased susceptibility to the development of CAD.

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Section: Discussionmentioning

confidence: 98%

Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients

et al. 2002

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“…NAD(P)H oxidase has been incriminated to mediate generation of ROS during AGE:RAGE interactions. The role of ROS in AGE:RAGE-mediated effects has been supported by studies demonstrating the inhibitory effect of antioxidants, such as, N-acetylcysteine, probucol, vitamin E and pyrrolidine dithiocarbamate on diabetic complications [113, 114]. …”

Section: Advanced Glycation End Products (Ages)mentioning

confidence: 99%

Oxidative Stress in Diabetic Nephropathy

Kashihara¹,

Haruna²,

Kondeti³

et al. 2010

CMC

415

266

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Diabetic nephropathy is a leading cause of end-stage renal failure worldwide. Its morphologic characteristics include glomerular hypertrophy, basement membrane thickening, mesangial expansion, tubular atrophy, interstitial fibrosis and arteriolar thickening. All of these are part and parcel of microvascular complications of diabetes. A large body of evidence indicates that oxidative stress is the common denominator link for the major pathways involved in the development and progression of diabetic micro- as well as macrovascular complications of diabetes. There are a number of macromolecules that have been implicated for increased generation of reactive oxygen species (ROS), such as, NAD(P)H oxidase, advanced glycation end products (AGE), defects in polyol pathway, uncoupled nitric oxide synthase (NOS) and mitochondrial respiratory chain via oxidative phosphorylation. Excess amounts of ROS modulate activation of protein kinase C, mitogen-activated protein kinases, and various cytokines and transcription factors which eventually cause increased expression of extracellular matrix (ECM) genes with progression to fibrosis and end stage renal disease. Activation of renin-angiotensin system (RAS) further worsens the renal injury induced by ROS in diabetic nephropathy. Buffering the generation of ROS may sound a promising therapeutic to ameliorate renal damage from diabetic nephropathy, however, various studies have demonstrated minimal reno-protection by these agents. Interruption in the RAS has yielded much better results in terms of reno-protection and progression of diabetic nephropathy. In this review various aspects of oxidative stress coupled with the damage induced by RAS are discussed with the anticipation to yield an impetus for designing new generation of specific antioxidants that are potentially more effective to reduce reno-vascular complications of diabetes.

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“…Hyperglycemia in diabetes can generate free radicals, hydrogen peroxide, and reactive ketoaldehydes by the auto-oxidation of glucose or from glycated proteins (3)(4)(5)(6)(7)(8). Many investigators have reported lower concentrations of glutathione in the erythrocytes, aorta, and lenses of diabetic patients compared with healthy subjects (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), except for some studies that reported similar glutathione concentrations (20).…”

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confidence: 99%

Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children.

2000

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OBJECTIVE -This study examined the relationship between cellular glutathione and vitamin E concentrations and the effect of vitamin E (␣-tocopherol) supplementation on glutathione and lipid peroxidation product concentrations in the erythrocytes of type 1 diabetic patients.RESEARCH DESIGN AND METHODS -We obtained written informed consent to participate in this study from diabetic patients (n = 29) and their age-matched nondiabetic siblings (n = 21) according to the guidelines of the Institutional Review Board on Human Experimentation. Diabetic patients were supplemented with a DL-␣-tocopherol (vitamin E) capsule (100 IU/ orally) or placebo for 3 months in a double-blind clinical trial. Fasting blood samples were collected from each diabetic patient before the start of and after the 3 months of vitamin E or placebo supplementation. Glutathione, malondialdehyde (which is a product of lipid peroxidation), and ␣-tocopherol were determined using high-performance liquid chromatography. A total of 5 diabetic patients were excluded after randomization from the data analyses. Data were analyzed statistically using a paired Student' s t test to compare 12 diabetic patients taking vitamin E with 12 diabetic patients receiving placebo supplementation and to compare diabetic patients with healthy nondiabetic subjects.RESULTS -Erythrocytes of diabetic patients had 21% higher (P Ͻ 0.001) malondialdehyde and 15% lower (P Ͻ 0.05) glutathione concentrations than healthy subjects. Vitamin E in erythrocytes had a significant correlation with the glutathione concentrations in the erythrocytes (r = 0.46, P Ͻ 0.02). Vitamin E supplementation increased glutathione concentrations by 9% (P Ͻ 0.01) and lowered concentrations of malondialdehyde by 23% (P Ͻ 0.001) and of HbA 1c by 16% (P Ͻ 0.02) in erythrocytes of diabetic patients. No differences were evident in these parameters before versus after placebo supplementation.CONCLUSIONS -Glutathione level is significantly related to vitamin E level, and supplementation with vitamin E (100 IU/day) significantly increases glutathione and lowers lipid peroxidation and HbA 1c concentrations in the erythrocytes of type 1 diabetic patients.

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Total Plasma Antioxidant Capacity Predicts Thrombosis-Prone Status in NIDDM Patients

Abstract: These findings are consistent with the hypothesis that oxidative stress may condition coagulation activation in diabetics. However, the data suggest that it is the total antioxidant capacity rather than any single plasma antioxidant that is the most relevant parameter.

Cited by 56 publications

References 41 publications

Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients

Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients

Oxidative Stress in Diabetic Nephropathy

Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children.

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