Soluble Lectin-Like Oxidized LDL Receptor 1 as a Possible Mediator of Endothelial Dysfunction in Patients With Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) defines a well-known cluster of metabolic disturbances associated with an increased risk of cardiovascular disease and diabetes. The aim of this study was to examine the distribution of soluble lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (sLOX-1) levels in patients with MetS, possible association of sLOX-1 with oxidized LDL (oxLDL), endothelial nitric oxide synthase (eNOS), nitric oxide (NOx), endothelin-1 (ET-1), paraoxonase 1 (PON1), and arylesterase (ARE) activities, and these parameters compared with healthy controls. METHODS: A total of 55 patients (37 women, 18 men) with MetS and 29 healthy controls (19 women, 10 men) with a body mass index (BMI) less than 25 kg/m(2) were enrolled in the study. RESULTS: sLOX-1, oxLDL, and ET-1 levels were significantly higher in patients with MetS than in control subjects (P = 0.023 P < 0.001, and P < 0.001, respectively). MetS patients have significantly lower eNOS and NOx levels, and PON1 and ARE activities than control subjects (P = 0.017, P < 0.004, P < 0.001, and P = 0.010, respectively). A positive correlation was observed between the sLOX-1 levels and the oxLDL, ET-1, BMI, glucose levels. ET-1 levels also exhibited significant negative correlation with ARE activity. CONCLUSION: sLOX-1 levels are associated with cardiovascular risk factors, such as increased oxLDL, obesity, and diabetes, in patients with MetS. An increased concentration of sLOX-1 could be an early predictor of endothelial damage in MetS. In addition, it appears that oxLDL, ET-1, eNOS, NOx, PON1, and ARE activities may accurately reflect the levels of endothelial dysfunction in MetS patients.

Relation of protein oxidation parameters and disease activity in patients with Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory vasculitis characterized by endothelial dysfunction, elevated reactive oxygen species (ROS), and neutrophil hyperfunction production including acute attacks and remission periods. Ischemia modified albumin (IMA), advanced oxidation protein products (AOPP), prooxidants-antioxidants balance (PAB), and ferric reducing antioxidant power (FRAP) were evaluated in regard to their role in the pathogenesis of BD as well as their relation to clinical presentation, uveitis attacks and remission periods, and healthy volunteers. METHODS: The study included 28 BD cases and 27 healthy volunteers as the control group. Blood samples were taken twice from each patient; first during an attack and second about three months after an attack, during remission period. RESULTS: AOPP, IMA and PAB levels were significantly increased in active periods of patients with BD compared with healthy control and remission periods of patients with BD (p < 0.0001, p < 0.0001, p < 0.0001, respectively). FRABP levels were found to be lower in active periods of patients with than healthy controls and remission periods of patients with BD (p < 0.001, p < 0.05, respectively). The AOPP levels were negatively correlated with the levels of FRAB in patients (r = -0.468, p = 0.012; r = -0.394, p = 0.038, respectively). The PAB levels were positively correlated with the levels of CRP in patients (r = -0.606, p = 0.001). CONCLUSIONS: Our results show that these parameters play a major role in the inflammatory reactions observed in BD. Increased levels of IMA and PAB are likely to be a result of inflammation-induced oxidative stress and hence its potential significance as a new marker of oxidative stress in BD.

Effects of omega-3 polyunsaturated fatty acid supplementation on serum fetuin-A levels in type 2 diabetic patients.

Fetuin-A is an endogenous inhibitor of the insulin-stimulated insulin receptor tyrosine kinase recently shown that high levels of circulating fetuin-A are associated with insulin resistance in humans suggesting that fetuin-A may represent a novel mechanism involved in the pathophysiology of type 2 diabetes (T2DM). Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to reduce triglyceride levels, but their impact on glycemic control are not well known. The aim of this study to determine the effects of omega-3 PUFA supplementation on fetuin-A and glycemic control in patients with type 2 diabetes mellitus. 40 T2DM patients (17 males/23 females; aged 39-65 years) were included in the study. Serum fetuin-A levels and metabolic and biochemical profiles were measured before (baseline) and two months after n-3 PUFA supplementations (1.2 g/day). Serum fetuin-A levels were measured by enzyme-linked immunosorbent assay. Our results indicated that serum fetuin-A, fasting glucose, HbA1c and triglyceride levels were significantly decreased after supplementation (P<0.02, P<0.001, P<0.02 and P<0.01, respectively). At baseline, serum fetuin-A levels were correlated with HbA1c (r:-0.391, P<0.04). A significant positive correlation between fetuin-A and both triglycerides (r: 0.343, P<0.05) and total cholesterol (r: 0.330, P<0.05) and negative correlation between fetuin-A and fasting glucose (r: -0.405, P<0.01) were found after the supplementations. When performed multiply regression analysis, we found that serum fetuin-a levels were related with triglyceride levels (r: 0.351, P<0.01) at baseline and HbA1c levels (r: 0.344, P<0.04) after the supplementation. Based on the results, it thought that omega-3 PUFA intake decreases serum fetuin-A levels and serum fetuin-A is associated with plasma lipids and glycemic controls in type 2 diabetic patients. Further studies are required to resolve the question.

Plasma AGE-peptides and C-peptide in early-stage diabetic nephropathy patients on thiamine and pyridoxine therapy.

AIM: The aim of the study was to evaluate circulatory AGE-peptide levels in diabetic nephropathy and to observe the effects of thiamine (vitamin B1) and pyridoxine (vitamin B6) therapy. METHODS: Type 2 diabetic patients (N.=57) were divided into two groups as "with nephropathy" (N.=27) and "without nephropathy" (N.=30). Diabetic nephropathy patients were treated with either B6 (N.=12) (250 mg/day) or B1+B6 (N.=15) (250 mg/day, each) for five months. At the beginning and the end of the experimentation period, glucose, HbA1c, triglyceride, cholesterol, insulin, C-peptide, thiamine pyrophosphate, pyridoxal phosphate and AGE- peptides were measured. RESULTS: AGE-peptides were higher in the diabetic group with nephropathy than without nephropathy (P=0.005). Within five months AGE-peptides increased in the diabetic group without nephropathy (P=0.042) but not in the group with nephropathy treated either with B1+B6 or B6. In B6 treated group a substantial decrease was observed in HbA1c (P=0.033). B1+B6 or B6 treatment both caused an increase in C-peptide (P=0.006, P=0.004). CONCLUSION: Among the parameters measured, plasma AGE-peptides was the only parameter found to be higher in type 2 diabetes mellitus patients "with nephropathy" than "without nephropathy". However, patients with nephropathy treated with B1+B6 or B6 did not display any further increase in AGE-peptides within five months. Both of the treatments caused an increase in C-peptide.

Increased DNA-glycation in type 2 diabetic patients: the effect of thiamine and pyridoxine therapy.

BACKGROUND: It is well known that advanced glycation plays an important role in the progression of diabetic complications. Although several studies have been done on protein glycation, studies related to DNA glycation is limited. The aim of this study is primarily to investigate DNA glycation in diabetes mellitus and secondarily to observe the effects of vitamins B(1) and B(6). MATERIALS AND METHODS: Patients with diabetes (n=31) were divided into 2 groups as patients with nephropathy (n=17) and without nephro-pathy (n=14). The control group was recruited from age and sex matched healthy individuals (n=30). In the experimental groups, DNA glycation was measured in DNA isolated from leukocytes. HbA(1c), thiamine pyrophosphate (TPP) and pyridoxal 5-phosphate (PLP) levels were determined in whole blood; glucose and insulin levels in plasma. Patients with nephropathy were further divided into 2 groups and were administered either vitamins B(1) + B(6) (n=6) or B(6) (n=11), for 5 months. All the measurements were performed both before and after the vitamin administration period. RESULTS: AGE-DNA levels were found significantly higher in diabetic patients (p<0.05) than the healthy controls. AGE-DNA and PLP levels were negatively correlated in control patients (r= - 0.361, p<0.05). The combined administration of B(1) and B(6) caused a significant decrease in AGE-DNA values (p<0.05). CONCLUSION: This study shows that the combined administration of vitamins B(1) and B(6) to diabetic nephropathy patients causes a decrease in DNA glycation in leukocytes. Importantly the administration of vitamin B(6) alone did not have such an effect. To our knowledge, these are the first reported findings related to glycation of leukocyte nuclear DNA in diabetic nephropathy.

Advanced glycation end products and antioxidant status in nondiabetic and streptozotocin induced diabetic rats: effects of copper treatment.

The effects of Cu(II) supplementation on glycemic parameters, advanced glycation end products (AGEs), antioxidant status (glutathione; GSH and total antioxidant capacity; TAOC) and lipid peroxidative damage (thiobarbituric acid-reactive substances, TBARS) were investigated in streptozotocin (STZ) induced diabetic rats. The study was carried out on Wistar albino rats grouped as control (n = 10), CuCl(2) treated (n = 9), STZ (n = 10) and STZ,CuCl(2) treated (n = 9). STZ was administered intraperitoneally at a single dose of 65 mg/kg and CuCl(2), 4 mg copper/kg, subcutaneously, every 2 days for 60 days. At the end of this period, glucose(mg/dl), Cu(microg/dl), TBARS(micromol/l), TAOC(mmol/l) were measured in plasma, GSH(mg/gHb) in erythrocytes and glycated hemoglobin (GHb)(%) in blood. Plasma AGE-peptides(%) were measured by HPLC flow system with spectrofluorimetric and spectrophotometric detectors connected on-line. Data were analyzed by the non-parametric Kruskal-Wallis and Mann-Whitney U test. In the STZ group glucose, GHb and AGE-peptide levels were all significantly higher than the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). CuCl(2) treated group had significantly lower glucose but significantly higher GHb, TAOC and TBARS levels than the control group (P < 0.05, P < 0.001, P < 0.05 and P < 0.001, respectively). STZ,CuCl(2) treated group had significantly higher GHb, TAOC and TBARS levels compared with the control group (P < 0.001, P < 0.05 and P < 0.05, respectively); but only TAOC level was significantly higher than the STZ group (P < 0.01). This experimental study provides evidence that copper intake increases total antioxidant capacity in both nondiabetic and diabetic states. However despite the potentiated antioxidant defence, lipid peroxidation and glycation enhancing effects of CuCl(2) are evident under nondiabetic conditions.

Biochemical evaluation of oxidative stress during exercise in patients with coronary heart disease.

The impact of exercise tolerance test on oxidative stress was assessed by thiobarbituric acid reactive substances and markers of antioxidant status, namely Cu Zn superoxide dismutase, glutathione peroxidase, glutathione and vitamin E in blood samples of patients with exertional angina. The study was aimed to differentiate patients with positive exercise test (coronary heart disease patients) from patients with negative exercise test, at rest and peak exercise with respect to the investigated variables. Significantly lower values for both glutathione peroxidase activity and glutathione level were observed in patients after exercise test (p<0.01 and p<0.05, respectively). Only the patients with positive exercise test had significantly lower values for Cu Zn superoxide dismutase, glutathione peroxidase and glutathione, and a significantly higher ratio of thiobarbituric acid reactive substances/glutathione after exercise, as compared to before (p<0.05, p<0.05, p<0.05, p<0.01, respectively). Our findings indicate that the exercise test applied to patients with exertional angina oxidatively stresses the erythrocytes to a greater extent in exercise test (+) patients than in exercise test (-) patients.

Secondary venous ischemic injury associated with neutrophil infiltration and lipid peroxidation: amelioration of injury by cyclosporin A in a rat inguinal island flap.

Secondary venous ischemia caused by anastomotic failure is one of the major causes of failure after free tissue transfers and replantations. The effects of cyclosporin A (CsA) on secondary ischemic injury associated with neutrophil infiltration and lipid peroxidation were evaluated in a rat inferior epigastric island skin flap model. Primary ischemia was produced by arteriovenous occlusion for 2 hours. Twenty-four hours later, secondary venous ischemia was produced by 5 hours of venous occlusion. Nonischemic (n = 5), primary ischemic (n = 5), and secondary ischemic control groups (n = 10), and four treatment groups (n = 10) were created. Treatment groups received either 15 or 30 mg per kilogram per day oral CsA for 3 days before flap elevation, or 15 or 30 mg per kilogram intravenous CsA at 4 hours of secondary venous ischemia. Flap survival area, malondialdehyde (MDA) content, and myeloperoxidase (MPO) activity were assayed for each group. The mean flap survival area of the high-dose posttreatment group was significantly higher than the secondary ischemic control group (29% +/- 39% vs. 3% +/- 8%; p < 0.05, Student's t-test). The MDA and MPO levels of each treatment group were significantly lower than the secondary ischemic control group at hours 1 and 24 (p < 0.0001, Student's t-test). The lowest MDA and MPO levels were achieved in the high-dose posttreatment group. Results suggest that CsA may improve flap survival after secondary venous ischemia by attenuating neutrophil infiltration and by reducing lipid peroxidation.

Calcium, magnesium, and zinc status in experimental hyperthyroidism.

In this study, experimental hyperthyroidism was established and used to investigate possible alterations in the calcium (Ca), magnesium (Mg), and zinc (Zn) homeostasis by assessing their concentrations in plasma and erythrocytes. In the L-thyroxine-induced hyperthyroidism condition, the experimental animals show a significant decrease in erythrocyte Ca, Mg, and Zn concentrations, and a significant decrease in plasma Mg concentration. Significant positive correlations were found for Mg and Zn both in plasma and in erythrocytes. The results suggest that the homeostasis of Ca, Mg, and Zn is altered during experimental hyperthyroidism.

Calcium, magnesium, and zinc status in experimental hypothyroidism.

In this study, experimental hypothyroidism was established and used to investigate possible alterations in the calcium, magnesium, and zinc homeostasis by assessing their concentration in plasma and erythrocytes. Hypothyroidism was induced by administration of methimazole an iodine blocker at a dose of 75 mg/100 g food for 3 wk. In the methimazole-induced hypothyroid state, the experimental animals showed a significant decrease in plasma zinc concentration, whereas a significant increase in plasma magnesium concentration occurred. No change was observed in plasma calcium concentration. The erythrocyte zinc and calcium concentrations were found to be increased, whereas magnesium concentration decreased. Erythrocyte magnesium concentration showed a significant positive correlation with T4 values. The study provides evidence for marked alterations in homeostatis of zinc, magnesium, and calcium.