Association between DNA strand breakage and oxidative, inflammatory and endothelial biomarkers in type 2 diabetes

Tatsch, Etiane; Bochi, Guilherme Vargas; Piva, Silvia; Carvalho, José Antônio Mainardi de; Kober, Helena; Torbitz, Vanessa Dorneles; Duarte, Thiago; Signor, Cristiane; Coelho, Adriane C.; Duarte, Marta Maria Medeiros Frescura; Montagner, Greice F.F.S.; Cruz, Ivana Beatrice Mânica da; Moresco, Rafael Noal

doi:10.1016/j.mrfmmm.2012.01.004

Cited by 65 publications

(42 citation statements)

References 37 publications

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“…This suggests a lower amount of damaged DNA fragments migrating from the nucleus, which is not what would be expected in the samples from subjects with diabetes. We had expected to observe a greater level of DNA damage due to a state of increased oxidative stress associated with diabetes [5]. Previous studies using the Comet assay on human whole blood samples to investigate DNA damage in obesity found a positive association between DNA damage, BMI, antioxidant status and MDA concentration [30].…”

Section: Discussionmentioning

confidence: 98%

“…In the case of increased levels of ROS, cells have defensive antioxidant systems that scavenge ROS and repair oxidative damage. Increased oxidative stress is associated with obesity and type 2 diabetes and increased DNA damage [4,5]. This association may be attributed to the role of oxidative stress in endothelial dysfunction, which plays a central role in both type 2 diabetes and obesity [6] Over recent years a number of measurements of oxidative stress have been developed, although few hold the reliability and specificity that is required for their use in a more clinical setting.…”

Section: Introductionmentioning

confidence: 99%

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Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes

Jones

Prior

Barry

et al. 2014

Diabetes Research and Clinical Practice

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes

Jones

Prior

Barry

et al. 2014

Diabetes Research and Clinical Practice

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“…Studies reported that NO x levels decrease [36,37], increase [38,39], or unchanged [40,41] in T2DM patients compared with control subjects. Our results regarding NO x levels are consistent with studies that found unchanged levels compared with healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…Our results regarding NO x levels are consistent with studies that found unchanged levels compared with healthy controls. Tatsch et al [37] found decreased serum NO x in T2DM and suggested that increased formation of O 2 •– during oxidative stress in vascular wall may inhibit NO-mediated endothelial function by formation of peroxynitrite. In the present study, no change in SOD activities were found in the diabetic groups from controls which may protect NO • from deleterious O 2 •– and so, NO x levels in diabetic patients did not differ from that of normal control.…”

Section: Discussionmentioning

confidence: 99%

Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients

et al. 2013

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BackgroundThe interaction of advanced glycation end products (AGEs) and its receptor (RAGE) has played an important role in the pathogenesis of diabetes and its complications. A soluble form of RAGE (sRAGE) has been reported as a decoy receptor for AGEs. Oxidative stress is demonstrated in pathological condition such as atherosclerosis and diabetes mellitus. It has been suggested to be involved in the pathogenesis of both macro- and microvascular complications. This study was designed to evaluate the effect of glycemic control on sRAGE and oxidative stress markers in type 2 diabetic patients.MethodsSeventy patients with type 2 diabetes and 20 healthy subjects were recruited into the study. Blood glutathione (GSH) and plasma total nitric oxide (NOx) levels were measured using commercially available colorimetric kits, blood superoxide dismutase (SOD) activity was measured by the method of Marklund and Marklund, and plasma C-peptide, oxidized LDL (ox-LDL), sRAGE, and VCAM-1 levels were measured using competitive ELISA kits.ResultsPlasma sRAGE levels were significantly lower (p < 0.05) while VCAM-1 levels were significantly higher (p < 0.05) in poorly controlled diabetic patients compared with healthy control. Blood GSH levels were significantly lower in diabetic patients compared with healthy control (p < 0.05). Plasma C-peptide, NOx, ox-LDL levels, and SOD activity were not significantly different in diabetic patients compared with healthy control. Plasma levels of sRAGE were negatively associated with circulating VCAM-1 levels in diabetic patients.ConclusionPoor glycemic control decreases plasma sRAGE and increases VCAM-1 levels while good glycemic control improves these abnormalities which provides benefit to diabetic patients.

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“…These patients are predisposed to developing vascular complications, nephropathy being one of the most common and dangerous (reviewed in [1]). DNA damage by endogenous free radicals and further ineffective repair of these lesions is considered to be one of the aetiological factors of DM [2,3]. Oxidative stress and abnormal production of nitric oxide (NO) are the main causes of an increased DNA breakage in DM.…”

mentioning

confidence: 99%

Effects of an Antimutagenic 1,4‐Dihydropyridine AV‐153 on Expression of Nitric Oxide Synthases and DNA Repair‐related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus

Ošiņa

Rostoka

Isajevs

et al. 2016

Basic Clin Pharma Tox

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Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein expression, while AV-153 (0.5 mg/kg) administration decreased it. AV-153 increased the expression of Parp1 gene in the kidneys of both intact and diabetic animals. Expression of H2afx mRNA and γH2AX histone protein, a marker of DNA breakage, was not changed in diabetic animals, but AV-153 up-regulated the expression of the gene without any impact on the protein expression. Development of DM was followed by a significant increase in iNOS enzyme expression, while AV-153 down-regulated the enzyme expression up to normal levels. iNos gene expression was also found to be increased in diabetic animals, but unlike the protein, the expression of mRNA was found to be enhanced by AV-153 administration. Expression of both eNOS protein and eNos gene in the kidneys was down-regulated, and the administration of AV-153 normalized the expression level. The effects of the compound in the kidneys of diabetic animals appear to be beneficial, as a trend for the normalization of expression of NO synthases is observed.

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Association between DNA strand breakage and oxidative, inflammatory and endothelial biomarkers in type 2 diabetes

Cited by 65 publications

References 37 publications

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes

Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients

Effects of an Antimutagenic 1,4‐Dihydropyridine AV‐153 on Expression of Nitric Oxide Synthases and DNA Repair‐related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus

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