The effects of n-3 long-chain polyunsaturated fatty acid supplementation on AGEs and sRAGE in type 2 diabetes mellitus.

In diabetes mellitus, chronic hyperglycemia leads to formation of advanced glycation end products (AGEs). Binding of AGEs to receptors of AGE (RAGE) causes deleterious effects. In populations with a high consumption of n-3 long-chain polyunsaturated fatty acids, a lower prevalence of diabetes mellitus has been reported. We aimed to investigate the effects of n-3 fatty acid (EPA and DHA) supplementation on the levels of AGEs (carboxymethyl lysine (CML) and pentosidine), sRAGE, and nuclear factor kappa B (NF-kB) in type 2 diabetes mellitus (T2DM). T2DM patients (n = 38) treated with oral hypoglycemic agents, without insulin were supplemented with n-3 fatty acids (1.2 g/day) for 2 months. Plasma CML, pentosidine, sRAGE, and NF-kB levels were measured by ELISA both before and after the supplementation. n-3 fatty acid supplementation significantly reduced fasting glucose (p < 0.01), glycated hemoglobin (HbA1c) (p < 0.05), and pentosidine (p < 0.05) levels. The supplementation induced percentage changes in pentosidine and HbA1c and in pentosidine and creatinine were observed to be correlated (r = 0.349, p < 0.05) and (r = 0.377, p < 0.05), respectively. Waist circumference and systolic and diastolic pressures were significantly decreased due to n-3 supplementation (p < 0.001, p < 0.01, p < 0.01), respectively. Our results show that supplementation with n-3 fatty acid has beneficial effects on waist circumference; systolic and diastolic blood pressures; and the levels of glucose, HbA1c, and pentosidine in T2DM patients. However, the supplementation failed to decrease these parameters to the reference ranges for healthy subjects. In addition, the supplementation did not appear to induce any significant differences in CML, sRAGE, or NF-kB.

Inflammatory hypothesis as a link between Alzheimer's disease and diabetes mellitus.

AIMS: The aim of the present study was to evaluate whether there was an inflammation-mediated link between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) status. METHODS: An age-matched control group and patient groups designated as AD without treatment (AD); AD under cholinesterase inhibitors (AD-CEI); DM without treatment (DM); DM under oral antidiabetic agents (DM-OAD); AD under treatment, who had newly diagnosed DM (AD-CEI+DM); and DM under treatment, who had newly diagnosed probable AD (DM-OAD+AD) were studied. Serum inflammation status was evaluated by the determination of serum C-reactive protein (CRP), tumor necrosis factor-alpha, interleukin (IL)-1ß and IL-6 levels. CRP levels were determined by an immunonephelometric method. The others were assayed by enzyme-linked immunosorbent assay methods. RESULTS: IL-1ß levels were found to be significantly lower in the DM group than in the control group (P < 0.01). The AD group had significantly higher serum IL-1ß levels than the DM group (P < 0.01). IL-6 levels were significantly higher in the AD and DM groups than in controls (P < 0.01 and P < 0.01). Serum tumor necrosis factor-alpha and CRP levels in the AD (P < 0.05 and P < 0.001, respectively) and DM groups (P < 0.05 and P < 0.001, respectively) were significantly higher when compared with the controls. The presence of AD or DM or therapies of the diseases did not significantly change in serum tumor necrosis factor-alpha levels. The AD-CEI + DM and DM-OAD+AD groups had significantly higher CRP levels than the AD-CEI group (P < 0.05) and DM-OAD groups (P < 0.001), respectively. Serum CRP levels showed a positive correlation with Mini-Mental State Examination scores (r = 0.339, P < 0.01). CONCLUSION: Our findings support the presence of a low-grade systemic inflammation link between AD and DM. Geriatr Gerontol Int 2016; 16: 1161-1166.

Lectin-like oxidised LDL receptor-1 as a marker of endothelial dysfunction in Behçet's disease.

OBJECTIVES: The aim of this study was to examine the distribution of lectin-like oxidised LDL receptor-1 (LOX-1) levels in patients with active BD, possible association of LOX-1 with the oxidised LDL (oxLDL), endothelial nitric oxide synthase (eNOS), nitric oxide (NO), endothelin-1 (ET-1) levels, and to characterise the differences between patients with active BD and those with systemic lupus erythematosus( SLE) in terms of these parameters compared with healthy controls. METHODS: A total of 30 patients with active BD, 22 patients with SLE as patients controls, and 30 healthy subjects were enrolled in this study. RESULTS: Significantly lower eNOS ve NO levels were observed in patients with BD and SLE compared with healthy controls. oxLDL, LOX-1 ve ET-1 levels were significantly increased in active periods of patients with BD and SLE compared with healthy control. There was no significant difference in oxLDL levels between subjects with BD and SLE. LOX-1 levels were significantly higher in active periods of patients with BD than in SLE , ET-1 levels were significantly lower. CONCLUSIONS: Endothelial dysfunction parameters are elevated in patients with BD having active disease. The necessary measures should be considered in terms of risk of atherosclerosis in BD, especially for the early identification of endothelial damage by looking at LOX-1 levels.

Serum brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3 levels in dementia.

The aim of this study is to measure serum levels of neurotropic factor (NF) in patients with dementia. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) were determined in Alzheimer's dementia patients without medication (AD; n: 22), Alzheimer's dementia patients receiving cholinesterase inhibitor (CEI) treatment (AD + CEI; n: 32) and vascular dementia patients receiving CEI treatment (VaD + CEI; n: 27) and the age-matched control group (n: 20). NGF levels were detected to be significantly higher in the control group than in AD group (P < 0.001). BDNF and NT-3 levels in AD group were not significantly different from control group's levels. NGF levels in AD + CEI group were significantly higher than in AD group (P < 0.05). There was also no significant difference in serum neurotrophic factor levels between AD + CEI and VaD + CEI group. A positive correlation between BDNF and Mini Mental State Examination (MMSE) scores (r: 0.422, P < 0.01) in AD group and a negative correlation between BDNF and MMSE scores in the AD + CEI group (r: -0.357, P < 0.005) were obtained. In conclusion, our results suggest that while serum NGF levels are associated with the presence of dementia, serum BDNF levels may be associated with the severity of Alzheimer's dementia. However, future studies are required to determine the importance of NFs.

Plasma oxidative and inflammatory markers in patients with idiopathic Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative disorder after alzheimer's disease. Neuroinflammation and oxidative damage are implicated to be responsible for the pathogenesis of neurodegenerative diseases. However, there are a few studies showing the changes in the biomarkers for neuroinflammation and oxidative damage in neurodegenerative diseases. In our study we aimed to examine the role of the molecules that are involved in oxidative stress and inflammation in PD patients taking L: -dopa treatment. Oxidized-LDL (ox-LDL), high-sensitivity C-reactive protein (hs-CRP) and the soluble intracellular adhesion molecule (ICAM) were chosen as biomarkers for systemic inflammation and oxidative damage. The patients were classified according to the Hoehn-Yahr staging system. Forty-five idiopathic L: -dopa-given PD patients and 25 age-matched healthy controls were examined. Plasma ox-LDL and ICAM levels were significantly higher in PD patients when compared with controls (p < 0.001 and p < 0.05, respectively). PD patients at all stages had significantly higher plasma ox-LDL levels than controls (p < 0.001). Plasma ICAM levels at stage 1 and 2 and CRP levels at stage 2 patients were significantly higher than controls (p < 0.05, p < 0.05, and p < 0.01, respectively). We insist that further studies have to be conducted to establish neuroinflammation and oxidative damage in PD. Establishing the roles of these pathological processes in PD might be the key to effective therapy at an early stage by antioxidants and/or anti-inflammatory drugs.

Acute phase response and oxidative stress status in familial Mediterranean fever (FMF).

We aimed to determine acute phase response (APR) and oxidative stress in patients with familial Mediterranean fever (FMF) and compare these characteristics with those in healthy controls; 20 patients with FMF and 15 healthy controls were enrolled in the study. The erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), fibrinogen, and leukocyte levels were determined as markers of APR. Thiobarbituric acid reactive substances (TBARS), conjugated diene, and lipid hydroperoxide levels were measured as markers of lipid peroxidation. Carbonyl group and thiol (T-SH) levels were analyzed to determine the oxidative damage to proteins, and 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to reflect DNA oxidation. The erythrocyte glutathione (GSH) level, and glutathione peroxidase (GSH-Px), CuZn superoxide dismutase (CuZn SOD), and catalase activities were measured as markers of antioxidant status. Conjugated diene (p < 0.001) and carbonyl group (p < 0.05) levels were significantly higher and GSH-Px activity (p < 0.01) was significantly lower in FMF patients compared with controls. FMF patients in the attack period (n = 8) had significantly higher CRP, ESR, fibrinogen, and leukocyte levels (p < 0.001) than patients in the attack-free period (n = 12). The T-SH level (p < 0.05) was significantly higher and CuZn SOD activity was significantly lower (p < 0.05) in FMF patients in the attack period. The findings revealed upregulated APR during the attack period in FMF patients and enhanced oxidative stress in the FMF patients as compared to controls.

Increased testicular 8-hydroxy-2'-deoxyguanosine (8-OHdG) and inducible nitric oxide synthetase (iNOS) and nuclear factor κB (NF-κB) expressions in experimental rat varicocele.

OBJECTIVES: To assess nuclear factor-kappaB (NF-kappaB), inducible NO synthase (iNOS) immunohistochemically, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) biochemically, which are sensitive biological markers of oxidative damage and stress, in testes with experimental varicocele. MATERIALS AND METHODS: Adult rats were randomly divided into three groups. Control group (n: 10), sham group (n: 10), varicocele group (n: 10). Of 14 rats undergoing partial ligation of the left renal vein, 10 rats had developed dilation of the left spermatic vein when evaluated 3 months after varicocele-inducing surgery. The rats were sacrificed after 3 months of the varicocele-inducing surgery. Ipsilateral and contralateral testes were examined for 8-hydroxy-2'-deoxyguanosine (8-OHdG) biochemically, inducible NO synthase (iNOS) and nuclear factor-kappaB (NF-kappaB) expression immunohistochemically. RESULTS: Inducible NO synthase (iNOS), nuclear factor-kappaB (NF-kappaB) expressions and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in both testes of varicocele group were markedly higher compared with control and sham groups (p < 0.01). There was no difference between control and sham groups (p > 0.05). CONCLUSIONS: Regarding to our results, we suggest that varicocele may produce oxidative stress in both of testes, and we believe that this stress may play a role in male fertility.

Oxidized LDL and anti-oxLDL antibody levels in peripheral atherosclerotic disease.

OBJECTIVE: Oxidative modification of LDL (oxLDL) is important in atherogenesis and is proposed as a useful marker for identifying patients with coronary artery disease. Antibody to oxLDL (oxLDL Ab) is detected in human sera, although its biological significance is not well established. We aimed to measure oxLDL and oxLDL Ab in peripheral atherosclerotic disease (PAD) patients, and to examine the relation between them in an attempt to understand the role of oxLDL Ab. Total risk of atherosclerosis was estimated using the global risk assessment score (GRAS) calculated on the basis of age, total cholesterol, HDL cholesterol (HDL-Chol), diabetes, hypertension and smoking. MATERIAL AND METHODS: Twenty-one patients aged 63.05+/-9.13 years, diagnosed by peripheric angiography as PAD, and 21 healthy controls aged 47.67+/-13.61 years took part in the study. Total LDL and HDL cholesterol levels were determined by enzymatic methods. Levels of circulating oxLDL were measured by monoclonal antibody 4E6-based competition ELISA. IgG class oxLDL Ab titre was measured by ELISA. RESULTS: Compared to healthy controls, PAD patients had higher levels of oxLDL (p<0.05), oxLDL Ab (p<0.05), LDL cholesterol (LDL-Chol) (p<0.05), total cholesterol (p<0.05) and lower HDL-Chol (p<0.05). OxLDL was found to be positively correlated with total cholesterol (r = 0.471, p<0.05) and LDL-Chol (r = 0.614, p<0.01) and GRAS (r = 0.435, p<0.05) and negatively with HDL-Chol (r = -0.459, p<0.05), but not with oxLDL Ab in PAD patients. CONCLUSIONS: These findings might indicate that high LDL-Chol levels influence the oxidation of LDL and that oxLDL is a possible marker of PAD. However, the role of oxLDL Ab in atherosclerosis remains controversial.

Homocysteine and nitric oxide in patients undergoing diagnostic coronary angiography.

We evaluated the plasma homocysteine (tHcy) and nitric oxide metabolites (nitrite plus nitrate; NOx) data of consecutive patients undergoing diagnostic coronary angiography (n=79) with respect to the presence and severity of coronary artery disease (CAD), the presence of acute coronary syndromes (ACS), and the risk status of patients. Hyperhomocysteinemia (>15 micromol/L) was detected in 11% of the controls (n=19) and 37% of CAD patients (n=60) (p=0.03). Plasma tHcy in CAD patients was not significantly different from controls, but those with 3-vessel disease had a significantly higher tHcy concentrations than did controls (p=0.049). The patients with 3-vessel disease and ACS had the highest concentrations of tHcy (16.9 +- 4.4 micromol/L), and the difference from the ACS patients with 1- and 2-vessel involvement was significant (p=0.03). In patients with 1-vessel involvement, tHcy was correlated with NOx (r=0.62, p=0.005); in patients with 2- and 3-vessel disease this correlation could not be observed. The high-risk patients (n=51) had a higher mean number of vessel involvement and tHcy (p<0.001, p<0.05, respectively) but lower NOx (p<0.05) when compared to the low-risk patients (n=28). It appears that in the early stages of atherosclerosis hyperhomocysteinemia causes an increase in NOx production, but with progression of the disease this compensatory increase disappears.

Oxidative damage to nuclear DNA in streptozotocin-diabetic rat liver.

1. Accumulating evidence suggests that oxidative and glycative stress is enhanced in diabetes. Oxidative stress induces DNA damage. In the present study, we assessed the 8-oxo-2'-deoxyguanosine (8-oxodG) content of DNA, an indicator of oxidative DNA damage, in streptozotocin (STZ)-induced diabetic (n = 21) and control rats (n = 18). 2. Rats were rendered diabetic by intraperitoneal administration of STZ at a dose of 65 mg/kg. Glucose was determined by glucose oxidase and glycated haemoglobin (GHb), an indicator of glycative stress, was determined by agarose-boronate affinity chromatography. 8-Oxo-2'-deoxyguanosine within the DNA (ratio of 8-oxodG to deoxyguanosine (dG)) was assessed by HPLC in conjunction with both electrochemical (8-oxodG) and diode array (dG) detection. 3. Glucose, GHb and the extent of oxidative DNA damage in the liver of STZ-diabetic rats were much higher compared with control rats. There was a correlation between GHb and 8-oxodG/10(5) dG levels in control (r = 0.756, P < 0.001) and diabetic groups (r = 0.468, 0.02 < P < 0.05). 4. These results clearly show that oxidative damage to hepatic nuclear DNA increases in the diabetic state and that this increase is correlated with glycative stress.

Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis.

AIM: Oxygen free radical mediated tissue damage is well established in pathogenesis of acute pancreatitis (AP). Whether nitric oxide (NO) plays a deleterious or a protective role is unknown. In alcohol-induced AP, we studied NO, lipooxidative damage and glutathione in pancreas, lung and circulation. METHODS: AP was induced in rats (n = 25) by injection of ethyl alcohol into the common biliary duct. A sham laparatomy was performed in controls (n = 15). After 24 h the animals were killed, blood and tissue sampling were done. RESULTS: Histopathologic evidence confirmed the development of AP. Marked changes were observed in the pulmonary tissue. Compared with controls, the AP group displayed higher values for NO metabolites in pancreas and lungs, and thiobarbituric acid reactive substances in circulation. Glutathione was lower in pancreas and in circulation. Glutathione and NO were positively correlated in pancreas and lungs of controls but negatively correlated in circulation of experimental group. In the experimental group, plasma thiobarbituric acid reactive substances were negatively correlated with pancreas thiobarbituric acid reactive substances but positively correlated with pancreas NO. CONCLUSION: NO increases in both pancreas and lungs in AP and NO contributes to the pathogenesis of AP under oxidative stress.

Oxidative damage to nuclear DNA in hyperthyroid rat liver: inability of vitamin C to prevent the damage.

The effects of hyperthyroidism on oxidative DNA damage in liver tissue and modification by vitamin C supplementation were investigated in rats. Animals were rendered hyperthyroid by administration of L-thyroxine (0.4 mg/100 g food) for 25 d. In the plasma samples, T(3), T(4), and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay and ascorbate spectrophotometrically. Oxidative damage to hepatic nuclear DNA was determined by measuring deoxy-guanosine (dG) and 8-oxodG by high-performance liquid chromatography with diode array detector electrochemical detection (HPLC-DAD-ECD). In hyperthyroidism, 8-oxodG/(10(5) dG) levels were significantly higher and plasma vitamin C levels lower than in control rats. The results of this experimental study show that oxidative damage to hepatic nuclear DNA increases in the hyperthyroid state and that vitamin C was not effective in preventing this damage.

Increased formation of 8-hydroxy-2'-deoxyguanosine in peripheral blood leukocytes in bladder cancer.

INTRODUCTION: Reactive oxygen species-induced damage to DNA plays a major role in carcinogenesis. METHODS: In order to estimate the level of oxidative damage in bladder cancer, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined in DNA isolated from peripheral blood leukocytes of healthy adults and patients with superficial transitional cell carcinoma. Patients with transitional cell carcinoma of the bladder and control individuals were similar in age. In this study, the level of 8-OHdG in DNA in male subjects was measured by the high-performance liquid chromatography-electrochemical detector method. RESULTS: The 8-OHdG levels in DNA from leukocytes of bladder cancer patients were significantly higher than those in controls. CONCLUSION: Reduction of oxidative stress is thought to be a very important measure for primary prevention of bladder cancer.

Hyperuricemia in hypothyroidism: is it associated with post-insulin infusion glycemic response?

This experimental study was designed to examine whether hyperuricemia in hypothyroidism is associated with insulin resistance. For induction of hypothyroidism, rabbits (n = 12) were administered methimazole orally (75 mg/100 g food) for 30 days. T3, T4 and TSH values measured in plasma prior to and at the end of the experimentation period revealed the establishment of hypothyroidism. In the euthyroid and hypothyroid states of rabbits, crystalline porcine insulin was administered (0.1 unit/kg body weight) intraperitoneally and plasma glucose was measured at 0, 15, 30, 45 and 60 minutes. Sum of post insulin infusion glucose values was considered to reflect insulin resistance. Creatinine clearance (GFR) and uric acid clearance (CuA) were determined. Additionally, triglycerides were measured in plasma and Mg2+ both in erythrocytes and in plasma. Due to hypothyroidism: i) The glycemic response to insulin was not altered. ii) GFR and CuA were both decreased but CuA/GFR unchanged. iii) Triglycerides in plasma decreased. iv) Mg2+ concentration increased in plasma whereas decreased in erythrocytes. Several associations were observed between the variables on correlation analysis. On the basis of our data, it could be suggested that insulin resistance does not exist in hypothyroidism. Hyperuricemia observed in hypothyroidism should be considered to be secondary to decreased renal excretion but not as an indicator of insulin resistance.