Hayder A. Al-Aubaidy

8-Hydroxy-2-deoxy-guanosine identifies oxidative DNA damage in a rural prediabetes cohort

Abstract Background: Rising levels of oxidative stress play an important role in the pathogenesis of type 2 diabetes mellitus. Therefore, we investigated the serum level of 8-hydroxy-2-deoxy-guanosine (8-OHdG) as an early oxidative stress marker in patients with prediabetes and with type 2 diabetes mellitus. Subjects and methods: Convenience sampling from people attending a diabetes screening clinic. Participants at the rural diabetes screening clinic had their medical history recorded as well as body mass index, blood glucose, cholesterol, glutathione, malondialdehyde, fasting blood glucose and 8-OHdG measured. Statistical analysis was performed using ANOVA followed by Sheffe posthoc test for between-group differences. Results: The 8-OHdG level was significantly greater in the prediabetes (516.5 ± 260 pg/ml) compared to control group (177.8 ± 91 pg/ml; P < 0.01). The diabetes group (1926.9 ± 1197 pg/ml) had the highest level of 8-OHdG, being approximately four times greater compared to the prediabetes group (P < 0.001). No significant change in the cholesterol profile, MDA level indicative of lipid peroxidation and antioxidant activity as measured by erythrocyte reduced glutathione was observed in the prediabetes group compared to the control group (P > 0.05). Conclusions: 8-OHdG levels in both the prediabetes and diabetes group were increased from control values suggesting a role for 8-OHdG as an early disease marker that may be more sensitive compared to cholesterol, MDA and erythrocyte reduced glutathione levels, which were within normal limits. This is of clinical significance as 8-OHdG is a strong indicator of oxidative stress related DNA damage within blood vessel walls and other tissue that increases the risk of cardiovascular disease.

Oxidative stress and triglycerides as predictors of subclinical atherosclerosis in prediabetes

Abstract Background The role of triglycerides in early preclinical atherosclerosis is controversial. Antioxidant markers may be associated with triglyceride levels in early preclinical atherosclerosis especially when fasting plasma glucose is raised. Methods This cross-sectional study included 127 participants attending the Diabetes Screening Clinic, Charles Sturt University, Australia. Results Serum 8-hydroxy-2-deoxy-guanosine (8-OHdG) was significantly greater in the impaired fasting glucose (IFG) group compared with the control group (536.7 pg/ml ± 249.8 versus 171.4 pg/ml ± 96.9, respectively). The increase in 8-OHdG was associated with a mildly non-significant elevation in low-density lipoprotein level (3.2 ± 1.1 mmol/l) and a poor level of high-density lipoprotein (1.31 ± 0.3 mmol/l) in the IFG group. However, a significant increase in triglycerides (1.6 ± 0.97 mmol/l; P < 0.05) in the IFG group was observed. Erythrocyte reduced glutathione (GSH) levels in the IFG group, although increased, were also not significantly different to control. Conclusion A significant increase in 8-OHdG is associated with increased levels of triglycerides in the absence of significant changes in reduced GSH and normal levels of cholesterol in the IFG cohort, suggesting that oxidative stress may be present and indicative of subclinical atherosclerosis.

Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes — Biomarkers as a possible tool for early disease detection for rural screening

OBJECTIVES This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes. DESIGN AND METHODS Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects. RESULTS While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant. CONCLUSIONS The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings.

Melatonin effects on myocardial ischemia–reperfusion injury: Impact on the outcome in patients undergoing coronary artery bypass grafting surgery

BACKGROUND Myocardial ischemia/reperfusion injury represents a clinically critical problem associated with coronary artery bypass graft surgery (CABG). The degree of oxidative stress, inflammation and apoptosis are increased during the reperfusion of the heart muscles following ischemia. The present study aims to examine the protective role of melatonin in ameliorating the degree of cardiac injury in patients undergoing bypass surgery, and whether this effect is a dose related. METHODS A total of forty-five patients who were undergoing elective CABG in (Al-Najaf Cardiac Center, Al-Najaf, Iraq) were included in this study for the period between January, 2015 and November, 2015. Participants were randomly allocated into 3 study groups: Placebo-controlled group (C), low dose melatonin treatment group, 10mg capsule once daily (M1) and high dose melatonin treatment group 20mg capsule once daily (M2). RESULTS Compared to the control group, there was a significant increase in the ejection fraction (EF%) associated with a significant decline in heart rate (HR) among the M1 and M2 groups compared to the C group (P<0.05). In addition, there was a significant reduction in plasma levels of cardiac Troponin-I (CTnI), interleukin-1beta (IL-1β), Inducible nitric oxide synthase (iNOS) and caspase-3 enzymes in the melatonin groups (group M1 and M2) compared to the control group, (P<0.05) in Melatonin-treated groups. Comparing the two melatonin study groups, the changes in the parameters mentioned above were more significant in the M2 group compared to the M1 group (P<0.05). CONCLUSION These findings suggested that melatonin supplementation can ameliorate the degree of myocardial ischemic-reperfusion injury, dose dependent effects.

Association of cardiovascular risk using non-linear heart rate variability measures with the framingham risk score in a rural population

Cardiovascular risk can be calculated using the Framingham cardiovascular disease (CVD) risk score and provides a risk stratification from mild to very high CVD risk percentage over 10 years. This equation represents a complex interaction between age, gender, cholesterol status, blood pressure, diabetes status, and smoking. Heart rate variability (HRV) is a measure of how the autonomic nervous system (ANS) modulates the heart rate. HRV measures are sensitive to age, gender, disease status such as diabetes and hypertension and processes leading to atherosclerosis. We investigated whether HRV measures are a suitable, simple, noninvasive alternative to differentiate between the four main Framingham associated CVD risk categories. In this study we applied the tone-entropy (T-E) algorithm and complex correlation measure (CCM) for analysis of HRV obtained from 20 min. ECG recordings and correlated the HRV score with the stratification results using the Framingham risk equation. Both entropy and CCM had significant analysis of variance (ANOVA) results [F(172, 3) = 9.51; <0.0001]. Bonferroni post hoc analysis indicated a significant difference between mild, high and very high cardiac risk groups applying tone-entropy (p < 0.01). CCM detected a difference in temporal dynamics of the RR intervals between the mild and very high CVD risk groups (p < 0.01). Our results indicate a good agreement between the T-E and CCM algorithm and the Framingham CVD risk score, suggesting that this algorithm may be of use for initial screening of cardiovascular risk as it is noninvasive, economical and easy to use in clinical practice.

Oxidative DNA damage: antioxidant response in postprandial hyperglycaemia in type 2 diabetes mellitus

The mechanism by which postprandial glucose load and sudden cardiac death are linked is not fully understood. This study compares the postprandial response of 8-hydroxy-deoxy-guanosine (8-OHdG)and erythrocyte glutathione (GSH) in control and type 2 diabetes groups. 8-OHdG was significantly elevated in type 2 diabetic patients (824.1±331.2 and 1087±273.1 pg/ml at the first and second hours respectively, p<0.05, versus 600.4±214.4 pg/ml at baseline) following a glucose load. This was associated with a significant reduction in the level of erythrocyte GSH after the first hour (59.1±9 mg/100ml; p<0.001) compared with the basal level (72.1±9 mg/100ml), followed by a significant elevation in the second hour (71.5±11.1 mg/100ml; p<0.001) com pared with the first hour, bringing the GSH level only back to base level. The increase in 8-OHdG in people with type 2 diabetes during the postprandial period further supports previous evidence of a defective antioxidant response and greater risk of heart attack due to blood vessel endothelial cell damage and smooth muscle proliferation. Br J Diabetes Vasc Dis 2011;11:87-91.

Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

Objective. This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p = 0.047) and a decrease of MCP-1 (−17.9%; p = 0.03). Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

Skeletal Muscle Microvascular-Linked Improvements in Glycemic Control From Resistance Training in Individuals With Type 2 Diabetes

OBJECTIVE Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin’s microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS Seventeen (11 male and 6 female; 52 ± 2 years old) sedentary patients with type 2 diabetes underwent 6 weeks of whole-body RT. Before and after RT, participants who fasted overnight had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced glycation end products) and underwent an oral glucose challenge (OGC) (50 g × 2 h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed body composition. RESULTS After RT, muscle MBF response to the OGC increased, while skin microvascular responses were unchanged. These microvascular adaptations were accompanied by improved glycemic control (fasting blood glucose, HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body mass and reductions in fasting plasma triglyceride, total cholesterol, advanced glycation end products, and total body fat. Changes in muscle MBF response after RT significantly correlated with reductions in fasting blood glucose, HbA1c, and OGC AUC with adjustment for age, sex, % body fat, and % lean mass. CONCLUSIONS RT improves OGC-stimulated muscle MBF and glycemic control concomitantly, suggesting that MBF plays a role in improved glycemic control from RT.

Cardiovascular Effects of Copper Deficiency on Activity of Superoxide Dismutase in Diabetic Nephropathy

Background: Copper (Cu) is essential both for its role in antioxidant enzymes, like Cu/zinc (Zn) superoxide dismutase (SOD) and ceruloplasmin, as well as its role in lysyl oxidase, essential for the strength and integrity of the heart and blood vessels. With such a central role in cardiovascular health, Cu has been generally overlooked in the debate over improving our cardiovascular health. Cu deficiency has produced many of the same abnormalities present in cardiovascular disease. It seems almost certain that Cu plays a large role in the development of this killer disease, not because of its excess in the diet, but rather its deficiency. Aim: This study was undertaken to investigate the cardiovascular effects of Cu deficiency on the activity of SOD in patients with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy. Materials and Methods: Fifty-five patients with T2DM were recruited in this study which were divided into two subgroups based on the presence of microalbuminuria, the first group (microal buminuric group, n = 31) had a microalbuminuria between 30 and 299 μg/mg. The second group (normoal buminuric group, n = 29) had an albumin level less than 30 μg/mg. The two diabetic groups were compared to the control group (n = 37). Results: The results of our study showed a significant reduction in the levels of SOD enzyme associated with an increased urinary Cu excretion in microalbuminuric group compared to the control group at P < 0.05. Conclusions: The current study illustrates that the regulation of the blood concentrations of Cu may be a potential therapeutic target for prevention and treatment of diabetic nephropathy.

Antiatherosclerotic potential of aliskiren: its antioxidant and anti-inflammatory effects in rabbits: a randomized controlled trial

Background: Aliskiren is a direct renin inhibitor. It counteracts renin-angiotensin system and is used to treat hypertension. This study aims to evaluate the effect of aliskiren on the progression of atherosclerosis in domestic rabbits. Methods: Twenty-one local domestic rabbits were divided into three groups each group had special dietary regimen for 8 weeks: Group I (normal control), Group II (atherogenic control) and Group III (2% Cholesterol + aliskiren 40mg/kg/day orally). Blood samples were collected at the end of experiment (8 weeks) for measurement of serum lipid profile, plasma high sensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA) and plasma reduced glutathione (GSH). Immunohistochemical analysis including vascular cell adhesion molecule-1 (VCAM-1); monocyte chemoattractant protein-1 (MCP-1); tumor necrotic factor - α (TNF-α); and interleukin – 17 (IL-17). Histopathologic assessment of aortic atherosclerotic changes were also performed. Results: Compared to normal control group, there is a significant increase in the level of lipid profile, hs-CRP (134.1±1.2ug/L), and malondialdehyde (0.561±0.136umol/L) in the atherogenic diet group, while GSH was significantly reduced (0.58±0.024mmol/L) at (p ≤ 0.05). Immunohistochemical analysis showed that expression of aortic VCAM-1; MCP-1; TNF-α; and interleukin–17 were significantly increased in atherogenic control group compared to normal control group (p<0.001). In addition, animals on atherogenic diet have significant atherosclerotic lesion compared to normal control group. Aliskiren group appears to have no significant effect on lipid profile compared to atherogenic control group, but it has statistically significant reduction in hs-CRP (73.1±3.88ug/L) and MDA (0.261±0.15umol/L) at (p ≤ 0.05). Aliskiren treatment failed to significantly increase the level of plasma reduced glutathione. In addition, aliskiren treatment significantly reduced the expression of VCAM-1; MCP-1; TNF-α; and IL–17 (p≤0.05). Histopathological examination of aortic arch showed that aliskiren significantly reduced atherosclerotic lesion (p≤0.005). Conclusion: We can conclude that aliskiren is helpful in reducing lipid peroxidation, systemic inflammation and aortic expression of inflammatory markers used in this study and hence reduces the progression of atherosclerotic plague.