The effects of genistein supplementation on fructose induced insulin resistance, oxidative stress and inflammation.

AIMS: This experimental study was designed to investigate the effects of 10weeks genistein administration on oxidative stress and inflammation in serum and liver of rats fed with fructose. MAIN METHODS: 6-8weeks old, 40 male Sprague-Dawley rats were included. Group 1 (control) was fed with standard chow food and 100µl/kg/day/rat dimethyl sulfoxide (DMSO) administered subcutaneously; group 2 (genistein) with standard chow food and 0.25mg/kg/day/rat genistein; group 3 (fructose) with standard chow food and drinking water 20% fructose, group 4 (fructose+genistein) with standard chow food, drinking water with 20% fructose and 0.25mg/kg/day/rat genistein. TNF-α, IL-6, visfatin as inflammatory markers and 8-isoprostane as a oxidative stress marker were measured by ELISA, glucose, triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol by enzymatic colorimetric method, AST and ALT by kinetic UV method. KEY FINDINGS: Significantly high 8-isoprostane levels in serum (p<0.001) and liver (p<0.05) in group 3 compared to control group indicate that presence of oxidative stress. Significantly high TNF-α and IL-6 levels in serum (p<0.05) and liver (p<0.01) and visfatin levels in serum (p<0.001) of group 3 indicate inflammation accompanying insulin resistance and oxidative stress. Genistein administration to fructose group causes a significant decrease in HOMA-IR (p<0.001) and LDLC (p<0.05) level. Significantly lower serum 8-isoprostane (p<0.01) level indicates the antioxidant effect of genistein and significantly lower liver TNF-α (p<0.01), serum, liver IL-6(p<0.01) and serum visfatin (p<0.01) levels reflect the antiinflammatory effects of genistein. SIGNIFICANCE: Genistein administration to rats fed with fructose causes an ameliorating effect on HOMA-IR values and lipid status markers in addition to its antioxidant and antiinflammatory effects.

The nesfatin 1 level in male patients with manic episode and alterations of nesfatin 1 level after antipsychotic and electroconvulsive treatment.

BACKGROUND: Nesfatin 1 is a newly identified peptide structured satiety hormone that is claimed to be responsible for the provision of appetite and metabolic regulation in hypothalamus. The change in appetite and energy is a well-known clinical feature of affective disorders and within treatment. We aimed to investigate serum nesfatin 1 level in patients with bipolar disorder who were in manic episode and the influences of treatment modalities on nesfatin 1 level. METHODS: Sixty eight patients were elected and were divided into two groups as: antipsychotic treatment (haloperidol 10-30 mg/daily+quetiapine 100-900 mg/daily) arm and ECT+antipsychotic treatment arm. And 30 healthy controls were included in the study. RESULTS: There was no significant difference according to mean age between patients and controls. Initial nesfatin 1 levels in patients and in both subgroups of patients were statistically lower than in healthy control group. The initial level of nesfatin 1 between ECT+antipsychotic and pure antipsychotic patient groups was not statistically significant. We found a trend of increment in nesfatin 1 level after treatment in both patient groups. CONCLUSIONS: This study is the first that revealed significantly lower nesfatin 1 level in manic episode than healthy controls. ECT+antipsychotic and antipsychotic treatments have no significant effects on nesfatin 1 level after manic episode treatment. These findings should be interpreted cautiously because of small sample size and being drug free only for one week.

Visfatin, Leptin, and TNF-α: Interrelated Adipokines in Insulin-Resistant Clinical and Subclinical Hypothyroidism.

PURPOSE: This study is designed to evaluate the interrelationships among adipokines-visfatin, leptin, and tumor necrosis factor-α (TNF-α)- and insulin resistance (IR) in overt (n = 40) and subclinic hypothyroid (n = 25) patients and compare our findings with sex and body mass index-matched healthy controls (n = 25). METHODS: Serum visfatin, leptin, and TNF-α levels were measured by enzyme-linked immunosorbent assay and C-reactive protein by immunoturbidimetry. Thyroid status (TSH, FT3, FT4) and lipid status (triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol) parameters were measured. IR was determined by homeostatic model assessment (HOMA-IR) and McAuley (McA) indices. RESULTS: HOMA-IR (p < 0.05) and McA indices (p < 0.01) revealed the presence of IR in overt hypothyroid patients. C-reactive protein, TNF-α, leptin, and visfatin levels were significantly higher (p < 0.01, p < 0.01, p < 0.001, and p < 0.001) in overt hypothyroid patients than euthyroid control group. Subclinic hypothyroid patients were observed to have significantly higher leptin and visfatin levels (p < 0.05) than euthyroid control group. In overt hypothyroid patients, we found plasma visfatin to be significantly positively correlated with HOMA-IR index (r = 0.336, p < 0.05) and body mass index (r = 0.445, p < 0.01) and negatively correlated with McA index (r = -0.574, p < 0.01). CONCLUSION: This study demonstrates the presence of IR in overt hypothyroid patients by HOMA and McA indices. Increased levels of visfatin, leptin, and TNF-α in overt and subclinic hypothyroid patients and the correlations among these adipokines highlighten their crucial role in the IR-associated disorders.

Osteoprotegerin, leptin and IL-6: association with silent myocardial ischemia in type 2 diabetes mellitus.

BACKGROUND: Diabetic patients often exhibit severe, asymptomatic coronary artery disease (CAD). The relationship between osteoprotegerin (OPG), inflammatory markers and silent myocardial ischemia remains to be elucidated. METHODS: We recruited 45 type 2 diabetic patients and 33 healthy controls and assessed them for silent myocardial ischemia (SMI) by myocardial perfusion imaging. Patient blood was tested for OPG, IL-6 and leptin concentrations. RESULTS: OPG, leptin and IL-6 levels were found significantly elevated in diabetic patients (p < 0.001, p < 0.01, p < 0.05). Based on our classification of presence/absence of SMI in our diabetic group, we found that there was a significant association between SMI and the biomarkers IL-6 (p < 0.001), leptin (p < 0.001) and OPG (p < 0.05). In multivariate regression analyses, OPG was found to be significantly related to diabetes mellitus and to SMI. Age, sex and smoking increased the association between OPG and SMI. CONCLUSION: High OPG, leptin and IL-6 levels are associated with the presence and severity of SMI in type 2 diabetic patients.

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.

Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis.

This study was designed to investigate the serum and synovial fluid leptin levels, and inflammatory markers in rheumatoid arthritis (RA) patients. Serum and synovial fluid leptin levels were significantly higher (P > 0.05) in RA patients than control group; RA patients with moderate disease activity (DAS < 2.7) having significantly higher leptin levels (P > 0.05) than those with low disease activity (DAS < 2.7). Leukocytes and erythrocyte sedimentation rate (ESR) were found to be significantly higher in moderate disease activity RA group compared to low activity group (P > 0.05, P < 0.001, respectively). Serum leptin level is found to be independent of age and inflammatory markers. ESR is positively correlated with DAS activity and CRP values. Our finding of no correlation between leptin and BMI shows that regulation of leptinemia is complex, and leptin levels cannot be used to assess RA activity.

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.

Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis.

OBJECTIVES: To investigate lipid, protein, DNA oxidation and antioxidant status in blood and synovial fluid of rheumatoid arthritis (RA) patients and to determine the importance of oxidative stress parameters in reflecting disease activity. DESIGN AND METHODS: 20 RA patients and 15 healthy controls were included. Lipid peroxidation (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide, and conjugated diene), protein oxidation (carbonyl and thiol), DNA oxidation (8-OHdG) and antioxidant status markers (glutathione (GSH), glutathione peroxidase (GSH Px), superoxide dismutase (CuZn SOD), and catalase) were determined in blood and synovial fluid. RESULTS: TBARS (p<0.001), lipid hydroperoxide (p<0.001), conjugated diene (p<0.001), carbonyl (p<0.001) and 8-OHdG (p<0.01) levels were significantly higher; thiol (p<0.01) and GSH levels (p<0.01) and GSH Px (p<0.001) and CuZn SOD (p<0.01) activities were significantly lower in blood of RA patients. TBARS (p<0.001), lipid hydroperoxide (p<0.001), conjugated diene (p<0.01), carbonyl (p<0.001) and 8-OHdG (p<0.05) levels were significantly higher, catalase activity (p<0.001) significantly lower in synovial fluid of RA patients. CONCLUSIONS: Increased lipid, protein and DNA oxidation markers and impaired antioxidant status confirm the role of oxidative stress in the pathogenesis of RA. Lipid peroxidation markers can serve as surrogate markers for disease activity.

Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to oxidative stress, nitric oxide pathway and homocysteine.

Hypercholesterolemia is characterized with changes in lipid profile, nitric oxide pathway and oxidative stress markers. This study is designed to evaluate the effects of hypercholesterolemic diet and atorvastatin therapy on oxidative stress, lipid peroxide and thiobarbituric acid reactive substances (TBARS), NO pathway markers, nitric oxide(NO) and asymmetric dimethylarginine (ADMA), homocysteine, and paraoxonase activity (PON1) in rabbits. Twenty rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups on the fourth week of the hypercholesterolemic diet. First group was fed with high-cholesterol diet alone, whereas the second group with the same cholesterol diet plus atorvastatin (0.3 mg/kg/day) for 4 weeks. High-cholesterol diet increased total cholesterol, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), ADMA, TBARS and lipid peroxide levels and reduced PON1 activity and NO levels in rabbits. Four weeks of atorvastatin therapy significantly increased HDL-C, PON1 activity and reduced LDL-C, TBARS and lipid peroxide concentrations. Atorvastatin therapy is beneficial in decreasing oxidative stress related with hypercholesterolemia, mainly affecting lipid profile and PON1 activity.

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.

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.

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.