Serum neurotrophic factor levels in patients with type 2 diabetes mellitus: relationship to metabolic syndrome components.

BACKGROUND: It has been thought that neurotrophins have metabotrophic effects and take part in the carbohydrate and lipid metabolism. The aim of the present study is to examine the levels of neurotrophins in type 2 diabetes mellitus (T2DM) and whether the levels are linked to the components of metabolic syndrome. METHODS: 90 patients and 35 healthy controls were enrolled in this study. The brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 were measured using an enzyme-linked immunosorbent assay. Plasma glucose, insulin, systolic blood pressure, diastolic blood pressure, and body mass index were measured, and, for each subject, the homeostasis model assessment of insulin resistance was calculated as the index of metabolic syndrome. RESULTS: The serum levels of brain-derived neurotrophic factor and neurotrophin-3 levels were higher, nerve growth factor lower in the T2DM patients than those of healthy controls (p < 0.001, p < 0. 001, and p < 0.001, respectively). The neurotrophic factor levels did not display any difference with respect to gender. The brain-derived neurotrophic factor was correlated with neurotrophin-3 level in female T2DM patients. In the male patients, brain-derived neurotrophic factor was correlated positively with plasma insulin and the homeostasis model assessment of insulin resistance; neurotrophin-3 was correlated positively with both systolic blood pressure and diastolic blood pressure, and nerve growth factor was correlated negatively with plasma glucose. CONCLUSIONS: We thought that the changes in the serum neurotrophic factor levels were associated with metabolic syndrome components in T2DM.

The association of oxidative stress markers with conventional risk factors in the metabolic syndrome.

BACKGROUND AND AIMS: The metabolic syndrome (MetS) is a common and complex disorder that consists of various abnormalities, including dyslipidemia, obesity, hypertension and hyperglycemia. We investigated the relationships between the levels of advanced protein oxidation products (AOPPs), the total antioxidant capacity (TAC) and the pro-oxidant-antioxidant balance (PAB) in MetS patients. METHODS: A total of 55 patients (37 women, 18 men) with MetS and 20 healthy controls (14 women, 6 men) with a body mass index (BMI) less than 25 kg/m(2) were enrolled in the study. Colorimetric methods were used to determine the levels of AOPPs, the TAC, and the PAB. RESULTS: AOPP, TAC, and PAB values were significantly higher in patients with MetS than in control subjects (p<0.001, p=0.050, and p<0.001, respectively). A positive correlation was observed between the AOPP levels and the glucose, triglyceride, insulin and HOMA-IR levels. PAB values also exhibited significant positive correlations with diastolic blood pressure and fibrinogen levels. Logistic regression analysis revealed that higher serum PAB values were positively and independently associated with the MetS (odds ratio: 1.110; 95% confidence interval: 1.006-1.224; P<0.37). CONCLUSIONS: Increased AOPP levels and higher PAB values are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive oxygen species. In addition, it appears that serum PAB values may accurately reflect the levels of oxidative stress in MetS patients.

Effects of methylene blue in reducing cholestatic oxidative stress and hepatic damage after bile-duct ligation in rats.

The aim of this study was to evaluate the effects of methylene blue against cholestatic oxidative stress and liver damage after ligation of the common bile duct in male Wistar rats. Eight animals were included in each of the following five groups: untreated control, methylene blue control, sham-operated, bile-duct ligation, and bile-duct ligation plus methylene blue. Methylene blue was administered intraperitoneally for 14 days at a daily dose of 2mg/kg per day. All rats were sacrificed 2 weeks following the experimental treatment and the livers of all groups were examined biochemically and histopathologically. The severity of cholestasis and hepatic injury were determined by changes in the plasma, including enzymatic activities: aspartate aminotransferase, alanine aminotransferase, gamma glutamine transferase, and also bilirubin levels. Malondialdehyde, nitric oxide and superoxide dismutase were measured to indicate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined as measures of neutrophil activation and collagen accumulation, respectively. Liver damage was significantly prevented in the bile-duct ligated rats treated with methylene blue compared with the control bile-duct ligated rats without methylene blue. Treatment with methylene blue markedly reduced activities of serum transaminase, gamma glutamine transferase and bilirubin levels as compared to bile-duct ligated rats without methylene blue. Positive immunolabelling for alpha-smooth muscle actin (alpha-SMA) was increased, especially in vascular smooth muscle cells, fibrotic septa and also around the proliferated bile ducts, after bile-duct ligation. Only weak alpha-SMA immunolabelling was seen in livers of rats treated with methylene blue. These results indicate that methylene blue can attenuate hepatic damage in extrahepatic cholestasis by reducing oxidative stress and inflammatory processes.

Effects of sphingosylphosphorylcholine against cholestatic oxidative stress and liver damage in the common bile duct ligated rats.

The goal of this study was to evaluate the possible protective effects of sphingosylphosphorylcholine (SPC) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. Fifty-six animals were included in each of the following 7 groups: control, SPC control, phosphate-buffered solution control, sham operated, bile duct ligation (BDL), BDL plus phosphate-buffered solution, and BDL plus SPC. Sphingosylphosphorylcholine was administered 14 days at a daily dose of 2 microm/mL intraperitoneally. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of aspartate aminotransferase, alanine aminotransferase, gama glutamin transferase, and levels of total bilirubin and direct bilirubin. Malondialdehyde, nitric oxide, and superoxide dismutase were determined to evaluate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined to assess neutrophil activation and collagen accumulation, respectively. Treatment with SPC markedly reduced serum transaminase activities as compared to BDL rats. Sphingosylphosphorylcholine also inhibited the increase in liver malondialdehyde; nitric oxide levels significantly and also attenuated the depletion of superoxide dismutase in the liver after BDL. Similarly, the increase in tissue myeloperoxidase activity and hydroxyproline owing to BDL was also attenuated by the SPC treatment. These data were supported by histopathologic findings. The alpha-smooth muscle actin-positive cells in the BDL were observed to be reduced with the SPC treatment. In conclusion, these findings suggested that SPC can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress, and inflammatory process. All these findings suggest that SPC may be a promising new therapeutic agent for cholestatic liver injury.

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.

Effects of vitamin E supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma.

This experimental study was designed to investigate the effects of vitamin E supplementation, especially on lipid peroxidation and antioxidant status elements 3/4 namely, glutathione (GSH), CuZn superoxide dismutase (CuZn SOD), and glutathione peroxidase (GSH Px), both in blood and liver tissues of streptozotocin (STZ) diabetic rats. The extent to which blood can be used to reflect the oxidative stress of the liver is also investigated. In diabetic rats, plasma lipid peroxide values were not significantly different,from control,whereas erythrocyte CuZn SOD (p < 0.01), GSH Px (p < 0.001) activities and plasma vitamin E levels (p < 0.001), were significantly more elevated than controls. Vitamin E supplementation caused significant decreases of erythrocyte GSH level (p < 0.01) in control rats and of erythrocyte GSH Px activity (p < 0.05) in diabetic rats. Liver findings revealed significantly higher lipid peroxide (p < 0.001) and vitamin E (p < 0.01) levels and lower GSH (p < 0.001), CuZn SOD (p < 0.001) and GSH Px (p < 0.01) levels in diabetic rats. A decreased hepatic lipid peroxide level (p < 0.01) and increased vitamin E/lipid peroxide ratio (p < 0.001) were observed in vitamin E supplemented, diabetic rats. A vitamin E supplementation level which did not cause any increase in the concentration of the vitamin in the liver or blood, was sufficient to lower lipid peroxidation in the liver. Vitamin E/lipid peroxide ratio is suggested as an appropriate index to evaluate the efficiency of vitamin E activity,independent of tissue lipid values. Further, the antioxidant components GSH, GSH Px and CuZn SOD and the relationships among them, were affected differently in the liver and blood by diabetes or vitamin E supplementation.

Iron supplementation in experimental hyperthyroidism: effects on oxidative stress in skeletal muscle tissue.

This study was designed to investigate the effects of iron supplementation on the parameters of oxidative stress in the skeletal muscle tissue of hyperthyroidism induced rats. Hyperthyroidism was found to cause an increase in thiobarbituric acid-reactive substances (TBARS) and copper zinc superoxide dismutase (Cu, Zn SOD) activity, but decreases in the glutathione-peroxidase (GSH Px) activity and glutathione (GSH). Iron supplementation caused an increase in TBARS and a decrease in GSH. Iron supplementation in hyperthyroid rats attenuated the hyperthyroid state, but lowered the plasma ferritin level, which is considered an indicator of thyroid hormone action. Iron supplementation caused no additional increase in the TBARS in hyperthyroid rats, ameliorated the decrease in GSH content and abolished the induction of Cu, Zn SOD. Our findings suggested no increase, but a decrease, in the risk of oxidative stress in iron supplemented hyperthyroid rats. Whether supplementation of iron would have similar effects in humans should be further investigated in clinical studies.

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.

Nitric oxide synthase inhibition by L-NAME in streptozotocin induced diabetic rats: impacts on oxidative stress.

The effects of nitric oxide synthase (NOS) inhibition by Nw-nitro-L-arginine methyl ester (L-NAME) administration on oxidative stress parameters were investigated in streptozotocin (STZ) induced diabetic rats. Lipid peroxidation as reflected by thiobarbituric acid reactive substances (TBARS) was insignificantly higher in diabetic rats. Plasma NO2+NO3 values (p < 0.05) and erythrocyte CuZn superoxide dismutase (CuZn SOD) and glutathione peroxidase (GSH Px) activities were significantly higher (p < 0.01, p < 0.001, respectively) in diabetic rats. L-NAME administration to diabetic rats caused significantly lower CuZn SOD and GSH Px activities (p < 0.01) and NO2+NO3 values (p < 0.001), whereas a significantly higher GSH level (p < 0.01). TBARS/GSH ratio was significantly higher in diabetic rats than controls (p < 0.05) and significantly lower in L-NAME administered diabetic rats than diabetic rats (p < 0.05). This experimental study highlightens the importance of NOS inhibition by L-NAME in the attenuation of oxidative stress in STZ diabetic rats.

Laryngeal cancer: in relation to oxidative stress.

This study was designed to investigate the oxidative stress parameters in laryngeal cancer and cancer-free adjacent tissues. Lipid peroxidation end product and the endogenous antioxidant components-CuZn superoxide dismutase (CuZn SOD) glutathione peroxidase (GSH Px), glutathione reductase (GSSG Rd) and glutathione (GSH)-were analysed by spectrophotometric and kinetic methods. Laryngeal cancer tissue exhibited higher lipid peroxidation than cancer free adjacent tissue. CuZn SOD and GSH Px activities and GSH level were significantly higher and GSSG Rd activity significantly lower in the cancer tissue. Detection of the antioxidant status may be useful to determine the tumour resistance to therapy, to choose the correct radiotherapy/chemotherapy and to monitor the effectiveness of the therapetic strategy.