Oxidative DNA damage correlates with carotid artery atherosclerosis in hemodialysis patients

Abstract

Oxidative stress is accepted as a nonclassical cardiovascular risk factor in chronic renal failure patients. The aim of this study was to evaluate the relation between oxidative DNA damage (8-hydroxy-2'-deoxyguanosine/deoxyguanosine [8-OHdG/dG] ratio), oxidative stress biomarkers, antioxidant enzymes, and carotid artery intima-media thickness (CIMT) in hemodialysis (HD) patients. Forty chronic HD patients without known atherosclerotic disease and 48 age- and sex-matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8-OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. 8-OHdG/dG ratios and MDA levels were higher; SOD and GPx activities were lower in HD patients compared to controls. HD patients had significantly higher CIMT compared to controls (0.61 ± 0.08 vs. 0.42 ± 0.05, p < 0.001). There was a significant positive correlation between CIMT and 8-OHdG/dG ratio (r = 0.57, p < 0.01) and MDA levels (r = 0.41, p < 0.01), while there was a significant negative correlation between CIMT and SOD (r = -0.47, p < 0.01) and GPx levels (r = -0.62, p < 0.01). It is firstly demonstrated that CIMT is positively correlated with oxidative DNA damage in HD patients without known atherosclerotic disease.

Correlations between Oxidative DNA Damage, Oxidative Stress and Coenzyme Q10 in Patients with Coronary Artery Disease

“…The higher activity of an antioxidant enzyme may be a compensatory regulation in response to increased oxidative stress. In our previous study, we demonstrated that 8-OHdG may be a good biomarker for risk assessment of subclinical cardiovascular disease in haemodialysis patients 24. DNA damage has been related with the development of cardiovascular pathologies in the general population, which is supported for the monoclonal origin of cells from human atherosclerotic plaques 25.…”

Emerging Roles of Mitochondria ROS in Atherosclerotic Lesions: Causation or Association?

“…13-16 8-OHdG accumulation has been observed in circulating leukocytes and in various cell types in atherosclerotic lesions of human and animal models. 15-18 We have recently shown that non-nuclear (mitochondrial) 8-OHdG exists in macrophages (Mac3 + cells) in aortic root lesions of WD-fed Ldlr -/- mice, and it is significantly associated with total atherosclerotic lesion area. 17 In line with this finding, a 5-kb mtDNA deletion, referred to as “the common mtDNA deletion,” has been identified in mouse and human atherosclerotic lesions and was found to be closely associated with the extent of atherosclerosis.…”

“…For example, HD patients were shown to have a significantly higher carotid artery intima media thickness (CIMT) compared with healthy controls, and the levels of SOD and GPX were negatively correlated with CIMT. 15 Another study showed that the specific activity of SOD2 in Apoe -/- mice exposed to second hand smoke was significantly decreased and mitochondria function was impaired. 24 In another study, endothelial cells isolated from type 2 diabetes mice had a lower level of SOD2 expression compared with non-diabetic controls, which was associated with a higher amount of mtROS and impaired endothelial function.…”

Evaluation of Assays for Measurement of Serum (Anti)oxidants in Hemodialysis Patients

“…Accumulation of uremic toxins [2], bioincompatibility of the dialyzer's membrane [3], depletion of low molecular antioxidants, in the first place ascorbic acid, during the hemodialysis session [4], and excessive and indiscriminate use of intravenous iron preparations [5] have been described as the main factors which cause oxidative stress in the chronically hemodialyzed patients. There is a large body of evidence that the prooxidant state of the chronically hemodialyzed patients is associated with cardiovascular disease [6–8], renal anemia [9, 10], and mineral and bone disorders [11], which largely contribute to their increased morbidity and mortality.…”