Hüseyin Avni Uydu

Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments

BACKGROUND Reactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. There is some evidence that the activation of immune-inflammatory process, increase of monoamines catabolism, and abnormalities in lipid compounds may cause overproduction of ROS and, in turn, antioxidative enzyme activities (AEAs) and lipid peroxidation (LP), and that these phenomena may be related to pathophysiology of major depression. METHODS The aims of this study were (i) to examine the AEAs and LP levels of the major depressed (MD) patients, and to compare these with healthy controls; and (ii) to investigate the effect of subchronic treatment with selective serotonin reuptake inhibitors (SSRIs) on AEAs and LP levels in MD subjects. Thirty MD patients, and 32 healthy controls (HC) participated in this study. AEAs and LP levels were determined by measuring several antioxidative enzymes and malondialdehyde (MDA) levels in plasma and/or in red blood cells. RESULTS Major depressed patients, especially melancholic patients, had higher AEA and LP levels than those of healthy controls. After treatment for 3 months with SSRIs, AEA and LP levels of the patients were significantly decreased to normal levels. CONCLUSION These findings suggest that (i) major depression, especially with melancholia, is associated with elevated AEAs and LP, and that (ii) subchronic treatment with SSRIs may have a suppressive effect on AEA and LP. CLINICAL IMPLICATION AND LIMITATION: AEAs might be used for monitoring SSRIs effects.

Plasma homocysteine and its relationships with atherothrombotic markers in psoriatic patients

BACKGROUND Hyperhomocysteinemia may constitute an independent risk factor for cardiovascular disease and may promote atherothrombosis. Psoriasis is one of the diseases associated with increased atherothrombosis. The aim of the present study was to examine serum total homocysteine (tHcy) level and its relationships with atherothrombotic markers. METHODS The study group included 30 patients with psoriasis (17 females and 13 males) with a mean age of 34.2 (age range: 27-40) and 30 sex and age matched healthy volunteers (15 females and 15 males) with a mean age of 36.7 (age range: 26-48). The concentrations of lipids, lipoproteins, acute phase reactants, tHcy and atherothrombotic markers [fibronectin, soluble vascular adhesion molecules-1 (sVCAM-1), soluble intercellular adhesion molecules-1 (sICAM-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), autoantibodies against oxidized LDL (AuAb-oxLDL)] were determined. RESULTS The mean levels of serum tHcy, fibrinogen, fibronectin, sICAM, PAI-1 and AuAb-oxLDL were increased in patients whereas tPA, vitamin B(12) and folate levels were decreased significantly. Increased levels of sVCAM were not statistically significant. tHcy levels were negatively correlated with vitamin B(12) (r=-0.40, P=0.027) and positively correlated with PAI-1 and AuAb-oxLDL levels (r=0.46, P=0.011; r=0.39, P=0.035, respectively). CONCLUSIONS It was concluded that the increased homocysteine concentration and altered endothelial cell-mediated proteins associated with increased lipids and LDL oxidation may play an important role for the development of atherothrombotic complications with psoriasis.

The evaluation of autoantibodies against oxidatively modified low-density lipoprotein (LDL), susceptibility of LDL to oxidation, serum lipids and lipid hydroperoxide levels, total antioxidant status, antioxidant enzyme activities, and endothelial dysfunction in patients with Behçet’s disease

OBJECTIVES Behçets disease is a multisystem disorder characterized by a chronic inflammation including acute attacks and remission periods. Decreased enzyme activity of the antioxidant system and increased levels of free radicals may have important roles in the damage of tissues observed in the disease period. In addition, the atherogenic tendency of serum lipid, lipoproteins, lipid peroxidation levels and endothelial dysfunction accompany the above mentioned findings. As a consequence of these events, different degrees of low density lipoprotein (LDL) oxidation occur in vivo, and then autoantibodies against oxidized-LDL(AuAb-oxLDL) are produced. DESIGN AND METHODS Lipids, lipoproteins, lipid hydroperoxide, AuAb-oxLDL, total antioxidant status (TAS), serum-soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor 1 (PAI-1) levels in serum, the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma, were determined in 25 patients with Behçets disease and in 25 healthy volunteers. Also, susceptibility to copper-induced in vitro oxidation of LDL by using lag time, a measure of resistance to oxidation, oxidation rate and extent of oxidation, a measure of diene production in both groups, was studied. RESULTS It was observed that lipid hydroperoxide and AuAb-oxLDL levels in patients with Behçets disease were significantly higher, but erythrocyte SOD, CAT, plasma GSH-Px activities, and TAS were significantly lower than those in healthy subjects. Susceptibility of LDL to oxidation in the patients was found to be increased. Total cholesterol, LDL-C and apo B levels and acute phase reactants were significantly higher, but HDL-C and apo AI levels were significantly lower, in patients when compared to healthy subjects. The levels of AuAb-oxLDL in patients were found to correlate with TAS, total cholesterol, LDL-C, lipid hydroperoxide and erythrocyte SOD activities (r = -0.62, p < 0.01; r = 0.64, p < 0.01; r = 0.55, p < 0.01; r = 0.81, p < 0.01; r = -0.63, p < 0.01, respectively). In addition, lipid hydroperoxide levels were found to correlate with total cholesterol, LDL-C and erythrocyte SOD activities (r = 0.45, p < 0.05; r = 0.45, p < 0.05; r = -0.46, p < 0.05, respectively). PAI-1 and sICAM-1 were found to be increased in the patients and correlated with AuAb-oxLDL and lipid hydroperoxide levels (r = 0.56, p < 0.01; r = 0.67, p < 0.01 and r = 0.59, p < 0.01; r = 0.61, p < 0.01, respectively). CONCLUSIONS It was concluded that the observed increase of lipid, lipoproteins, lipid hydroperoxide, susceptibility of LDL to oxidation, autoantibodies against ox-LDL levels and decrease of antioxidant enzyme activities and total antioxidant status and increased secretion of endothelial derivated peptides including sICAM and PAI-1, and their interactions may indicate that there is a tendency to atherothrombotic events in patients with Behçets disease.

Decreased nitric oxide end-products and its relationship with high density lipoprotein and oxidative stress in people with type 2 diabetes without complications

Diabetes mellitus is associated with hyperglycaemia, hyperlipoproteinaemia, increased oxidative stress and decreased nitric oxide production from endothelial cells. In the present study the aim was to determine the relationships between serum lipids, lipoproteins, erythrocyte malondialdehyde (eMDA), as a marker for oxidative stress, and serum nitrite and nitrate levels, as degradation products of nitric oxide in type 2 diabetic patients without complications. The study group included 30 patients and 30 sex- and age-matched healthy volunteers. Total cholesterol, triacylglycerol, LDL cholesterol, apo B, HbA(1c) and glucose levels in patients were significantly higher than in controls, and HDL cholesterol levels lower. Increased eMDA levels and decreased nitrate and nitrite+nitrate levels (+/-SD) were observed in patients compared to controls (87+/-22 vs 59+/-17 nmol/g-Hb (P<0.01); 11.8+/-8.6 vs 22.8+/-10.8 micromol/l (P<0.01); and 16.8+/-11.0 vs 28.8+/-11.3 micromol/l (P<0.01), respectively). When the patients were divided into two groups according to HDL cholesterol levels (< or =0.91 and >0.91 mmol/l), total plasma nitric oxide end-products were found to be decreased in patients with low HDL levels compared to those patients with high HDL levels [men, 11.7+/-6.4 vs 24.6+/-14.9 micromol/l (P<0.01); women, 12.5+/-6.6 vs 21.4+/-6.6 micromol/l (P<0.01]. Nitrite and nitrate levels were correlated with HDL cholesterol (r=0.50, P<0.05) and eMDA (r=-0.52, P<0.05). It was concluded that the patients with unregulated blood glucose levels have abnormal lipid and lipoprotein metabolism and decreased nitric oxide end-products, with relationships between nitric oxide products and dyslipidaemia, especially between low HDL cholesterol levels and increased oxidative stress.

The effects of lipid-lowering therapy on low-density lipoprotein auto-antibodies: relationship with low-density lipoprotein oxidation and plasma total antioxidant status

BackgroundOxidized low-density lipoprotein (Ox-LDL) is believed to play an important role in the progression of atherosclerosis. Oxidative modification of low-density lipoprotein (LDL) is a prerequisite for rapid accumulation of LDL in macrophages and for the formation of foam cells. Because of high antioxidant levels in plasma, LDL oxidation is suggested to occur mainly in the subendothelial space of the arterial wall, where there is the concomitant presence of large amounts of reactive oxygen species generated by endothelial cells and activated leukocytes. After Ox-LDL formation, antibodies against this form of LDL may occur. Auto-antibodies against Ox-LDL (AuAb-Ox-LDL) show directly in in-vivo LDL oxidation. Many studies have indicated that the amount of antibodies in serum is positively correlated to the rate of progression of atherosclerotic plaques. Design and methodsIn this study the effect of lipid-lowering therapy on the levels of AuAb-Ox-LDL in patients with dyslipidemia was determined using atorvastatin (10 mg/day), and the relationship between the antibodies and plasma total antioxidant status (TAS) and LDL oxidation capacity was also investigated. Serum levels of AuAb-Ox-LDL, lipids, lipoproteins, TAS and susceptibility of LDL to oxidation were determined using lag time in 44 patients with dyslipidemia (29 with hypercholesterolemia and 15 with mixed-type hyperlipidemia). ResultsAfter lipid-lowering therapy, serum levels of AuAb-Ox-LDL were found to be significantly decreased, by 18.7%, while lag time and plasma TAS were increased (31.3% and 7.6% respectively) in patients with dyslipidemia. The percentage change in lag time was found to be negatively correlated to the percentage change in AuAb-Ox-LDL (r  = −0.31, P  < 0.05). The percentage change in lag time also showed a positive correlation with the percentage change in TAS (r  = 0.58, P  < 0.01). AuAb-Ox-LDL levels decreased by 21.7% in patients with hypercholesterolemia and by 12.6% in patients with mixed-type hyperlipidemia. Also AuAb-Ox-LDL levels in patients with hypercholesterolemia were higher than in those with mixed-type hyperlipidemia (367 ± 294 compared with 300 ± 176 mU/l). ConclusionIt was concluded that lipid-lowering therapy may contribute to the reduction in levels of AuAb-Ox-LDL and the increase in the antioxidant capacity of plasma LDL and TAS. It was also suggested that the measurement of antibodies against Ox-LDL during lipid-lowering therapy may be used as an important marker for representing in-vivo LDL oxidation and atherosclerotic processes.

Relationship between lipid peroxidation and disease activity in patients with Behçet's disease.

Behçets disease is a chronic multi-systemic disorder which is characterized by a relapsing systemic inflammatory process. The alteration of lipid profile and lipid peroxidation resulting from the inflammatory process may he associated with an increased risk for atherosclerosis in patients with Behcets disease. We investigated lipids, lipoprotein and lipid peroxidation and their inter-relationships considering the disease activity. Eighteen patients (11 male and 7 female) and 20 age-matched healthy subjects (10 male and 10 female) were studied. Lipid profile including total cholesterol, triacylglycerol, HDL-cholesterol, LDL-cholesterol, lipoprotein(a), apoAI and apoB, and acute phase reactants including polymorphonuclear (PMN) elastase, PMN leukocyte count, erythrocyte sedimentation rate (ESR) and complements (C3, C4) were evaluated in patients in active and inactive periods of Behçets disease and control subjects. The levels of thiobarbituric acid reactive substance (TBARS) were assessed as an indicator of lipid peroxidation. Lipid peroxidation was found to he increased in the active period compared to the inactive period of the disease and control subjects. Also, lipid peroxidation showed correlations of various degrees with atherogenic lipid parameters in both periods of the followed-up patients. In conclusion, patients with Behçets disease in the active period may be much more susceptible to atherogenic events than those in the inactive period of the disease and control subjects.

Plasma fibronectin level and its relationships with lipids, lipoproteins and C-reactive protein in patients with dyslipidaemia during lipid-lowering therapy

Objectives — The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy. Methods — Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day. Results — After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43,6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=–0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57±0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57±0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45±0.11 g/l). During the lipidlowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased. Conclusions — It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.OBJECTIVES The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy. METHODS Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day. RESULTS After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43.6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=-0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57 +/- 0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57 +/- 0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45 +/- 0.11 g/l). During the lipid-lowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased. CONCLUSIONS It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.

The effects of royal jelly on the oxidant-antioxidant system in rats with N-methyl-N-nitrosourea-induced breast cancer

Abstract Objectives: To determine the effect of royal jelly (RJ) on the oxidant-antioxidant balance in rats with N-methyl-N-nitrosourea (MNU) induced breast cancer and to compare this with the chemotherapeutic agent paclitaxel. Material and methods: Fifty-six female Sprague Dawley rats were divided into five groups. Except control group (n=8, Group I) others received MNU (50 mg/kg, a single dose, i.p.) to develop breast cancer: Group II (n=8) untreated, Group III (n=7) treated with paclitaxel (15 mg/kg/week, 3 times, i.p.), Group IV (n=7) with RJ (by oral gavage, 100 mg/kg/day, for 30 days), and Group V (n=7), with paclitaxel+RJ. At the end of 30 days, histopathological and biochemical parameters were evaluated in breast tissues. Results: Levels of protein carbonyl (PC) and 8-hydroxy-deoxyguanosine (8-OHdG) were higher in Group V than in Group II while malondialdehyde (MDA) levels were lower in groups IV and V compared to Group II (p<0.05). Levels of catalase (CAT) in Group V and glutathione (GSH) in Group III were higher than Group II (p<0.05). Glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels did not significantly different. Decreasing effect of RJ on CA15-3 levels was relevant to histopathological results. Conclusion: Although RJ (with or without paclitaxel) had increasing effect of antioxidant status it was insufficient to reduce oxidative stress in breast cancer.