Tevfik Sabuncu

Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease

OBJECTIVES To determine oxidant and antioxidant status in women with polycystic ovary syndrome (PCOS) and its contribution to the risk of cardiovascular disease. DESIGN AND METHODS 27 women with PCOS were compared with regard to oxidant and antioxidant status with 18 age- and body mass index (BMI)-matched healthy. Oxidant status was evaluated by determination of erythrocyte malondialdehyde (MDA) concentration, while antioxidant status was evaluated by determination of erythrocyte reduced glutathione (GSH) concentration, and glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Area under curve (AUC) for glucose, AUC for insulin and the insulin sensitivity index (ISI) were calculated from two-hour OGTT. RESULTS Women with PCOS were found to have higher AUC for glucose (p = 0.01), AUC for insulin (p < 0.001), MDA level (p = 0.009) and SOD activity (p = 0.04), and lower ISI (p < 0.001) and GSH level (p = 0.03) than the controls. In correlation analysis, a significant relationship was found between MDA levels and age (p < 0.01), BMI (p < 0.001), waist-to-hip ratio (p < 0.01), systolic and diastolic blood pressures (both p < 0.05), AUCs for glucose and insulin (both p < 0.05), ISI (r = -0.42, p < 0.05) and triglyceride (p < 0.01). CONCLUSIONS An increase in oxidant status was found in women with PCOS, and this increase was related to central obesity, age, blood pressure, serum glucose, insulin and triglyceride levels and insulin resistance. In contrast, antioxidant status was observed to be insufficient. These findings suggest that increased oxidative stress may contribute to the increased risk of cardiovascular disease in women with PCOS.

Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats

Although melatonin has been established as a free radical scavenger and antioxidant, its effects in diabetes have not been thoroughly investigated. The purpose of this study, therefore, was to investigate the effects of melatonin administration on lipid peroxidation and antioxidant status in streptozotocin (STZ)‐induced diabetes in rats. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) were compared in 3 groups of 10 rats each [control non‐diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)]. In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60‐mg/kg dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10‐mg/kg i.p. dose of melatonin per day. After 6 wk, the rats in groups II and III had significantly lower body weights and significantly higher blood glucose levels than the rats of group I (P<0.001 and P<0.001, respectively). There were no significant differences in body weight or blood glucose levels between groups II and III. MDA levels in untreated diabetic rats were higher than those in control group rats and in diabetic rats treated with melatonin (P<0.01 and P<0.05, respectively). However, MDA levels in diabetic rats treated with melatonin were not different from those of the control group. The GSH, GSH‐Px and SOD levels of untreated diabetic rats were significantly lower than those of the control group (P<0.02, P<0.002 and P<0.05, respectively). In group III, however, melatonin prevented decreases in the thiol antioxidant and the associated enzymes, and so these levels were not significantly different from those in the control group. These results confirm the presence of oxidative stress in STZ‐induced experimental diabetes and indicate the beneficial free radical‐scavenging and antioxidant properties of melatonin.

Sibutramine has a positive effect on clinical and metabolic parameters in obese patients with polycystic ovary syndrome

OBJECTIVE To evaluate the effectiveness of sibutramine therapy alone and in combination with ethinyl estradiol-cyproterone acetate (EE-CPA) on the clinical and metabolic parameters of obese women with polycystic ovary syndrome (PCOS). DESIGN Prospective randomized, controlled study. SETTING Endocrinology and gynecology clinics. PATIENT(S) Forty obese women with PCOS. INTERVENTION(S) Group 1 was treated with oral EE-CPA (35 microg-2 mg/day), group 2 with oral sibutramine (10 mg/day), and group 3 with a combination of EE-CPA plus sibutramine for 6 months. All groups were advised to consume a diet of 1200 kcal/day. MAIN OUTCOME MEASUREMENT(S) Measurements were performed before and 6 months after treatment of body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, Ferriman-Gallwey hirsutism score, total testosterone, free testosterone, sex hormone-binding globulin, dihydroepiandrosterone sulfate (DHEAS), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose and insulin during oral glucose tolerance test, and insulin sensitivity index; area under the curve for glucose and insulin were obtained from OGTT. RESULT(S) Body mass index, Ferriman-Gallwey hirsutism score, serum total testosterone, free testosterone, and DHEAS levels were significantly decreased and SHBG was significantly increased in all groups at the end of the study. WHR, diastolic blood pressure, and serum triglyceride level were significantly reduced only in the sibutramine group. CONCLUSION(S) Sibutramine might have a positive effect on hyperandrogenemia, and clinical and metabolic risk factors for cardiovascular disease in obese women with PCOS.

Measurement of the total antioxidant response using a novel automated method in subjects with nonalcoholic steatohepatitis

BackgroundOxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the total antioxidant response using a novel automated method in nonalcoholic steatohepatitis subjects. As a reciprocal measure, we also aimed to determine total peroxide level in the same plasma samples.MethodsTwenty-two subjects with biopsy proven nonalcoholic steatohepatitis and 22 healthy controls were enrolled. Total antioxidant response and total peroxide level measurements were done in all participants. The ratio percentage of total peroxide level to total antioxidant response was regarded as oxidative stress index.ResultsTotal antioxidant response of subjects with nonalcoholic steatohepatitis was significantly lower than controls (p < 0.05), while mean total peroxide level and mean oxidative stress index were higher (all p < 0.05).In subjects with nonalcoholic steatohepatitis, fibrosis score was significantly correlated with total peroxide level, total antioxidant response and oxidative stress index (p < 0.05, r = 0.607; p < 0.05, r = -0.506; p < 0.05, r = 0.728, respectively). However, no correlation was observed between necroimflamatory grade and those oxidative status parameters (all p > 0.05).ConclusionNonalcoholic steatohepatitis is associated with increased oxidant capacity, especially in the presence of liver fibrosis. The novel automated assay is a reliable and easily applicable method for total plasma antioxidant response measurement in nonalcoholic steatohepatitis.

Non-diabetic metabolic syndrome and obesity do not affect serum paraoxonase and arylesterase activities but do affect oxidative stress and inflammation

OBJECTIVE Paraoxonase-1 (PON-1), which has PON and arylesterase activities, is a high-density lipoprotein (HDL)-bound antioxidant enzyme that inhibits atherosclerosis. Diabetes has been shown to have an impact on oxidative stress. The effect of metabolic syndrome (MetS) on oxidative stress and PON-1 has been shown before, and PON-1 has been found to be related with accelerated atherogenesis. This study aimed to determine the oxidative state and PON and arylesterase activities in non-diabetic MetS and non-MetS obese patients. DESIGN Thirty obese patients (3 M and 27 F) without MetS, 40 non-diabetic obese patients (3 M and 37 F) with MetS, and 30 controls (2 M and 28 F) were enrolled. METHODS A 75 g glucose tolerance test was performed. PON-1, PON, arylesterase, total antioxidant status (TAS), high-sensitive C-reactive protein (hsCRP), and metabolic parameters were analyzed. RESULTS PON and arylesterase activities were similar between the groups, while TAS was low in both MetS and obese groups compared to controls (P<0.01 and P<0.05 respectively). CRP was higher in the MetS group compared with the obese and control groups (P<0.01 and P<0.001 respectively). In both the obese and MetS groups, CRP showed a positive correlation with body mass index (BMI). TAS was negatively correlated with BMI, waist circumference, triglyceride levels, and systolic and diastolic blood pressures (P<0.001). CONCLUSIONS Oxidative stress is altered in non-diabetic MetS and non-MetS obese patients, but PON and arylesterase activities seem not to be affected. This result may be due to the absence of diabetes, the most severe form of altered carbohydrate metabolism.

Metabolic syndrome prevalence according to ATP III and IDF criteria and related factors in Turkish adults.

Introduction The aim of this study is to investigate the prevalence of metabolic syndrome (MS) and its components according to Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria and the risk factors affecting MS. Metabolic syndrome prevalence was evaluated according to certain quintet age groups, altitude, location and demographic features. Material and methods This study was a cross-sectional survey conducted in 24 provinces from the 7 regions of Turkey. A total of 4309 adults from 7 regions participated in the study (1947 males, 45.2%). Results The mean age of participants was 47 ±14 years. Metabolic syndrome prevalence was found as 36.6% according to ATP III and 44.0% according to IDF. The MS rate was found to be higher in females compared to males in both groups (p < 0.01). According to both criteria, MS prevalence was found to be higher in subjects who lived in coastal regions when evaluated according to altitude and in subjects who lived in district centers when evaluated according to location. The MS risk is 1.62-fold higher in females compared to males. Metabolic syndrome risk increases as age increases and is highest in the 61-65 age group. Metabolic syndrome risk increases 2.75-fold in the overweight compared to normal weighing subjects and 7.80-fold in the obese. Conclusions Metabolic syndrome prevalence was found to be high in Turkey according to both criteria. Metabolic syndrome prevalence increases as age and body mass index (BMI) increase. Age, female gender and obesity are independent risk factors for MS development.

The effects of atorvastatin and rosuvastatin on oxidative stress in diabetic patients.

AIM Diabetes is associated with abnormalities in lipid profile and increased oxidative stress. Statins are preferred agents in diabetic patients due to their antioxidant and LDL-C lowering effects. This study is designed to compare the effects of atorvastatin and rosuvastatin on low density lipoprotein cholesterol (LDL-C), lipid hydroperoxide (LOOH), total oxidant status (TOS) and total antioxidant capacity (TAC) in diabetic patients with hyperlipidemia. MATERIALS AND METHODS Sixty two patients who have type 2 diabetes mellitus with serum LDL levels more than 100mg/dL were randomly assigned to receive atorvastatin 20mg (n=31) or rosuvastatin 10mg (n=31). Blood tests were performed at the beginning of the study and after three months. RESULTS There were no statistically significant differences in the pre- and after treatment levels of the LDL-C between groups. TAC values were increased in both groups and statistically significant in the former group (p=0.007). There was no difference between the change percentages ((after treatment TAC-pretreatment TAC)/pretreatment level) of TAC between two treatment groups. The effects of two drugs on the other oxidative parameters were not significantly different. CONCLUSION Both atorvastatin and rosuvastatin may be helpful in reducing increased oxidative stress in diabetic patients with hyperlipidemia.

EARLY CHANGES IN PARAMETERS OF BONE AND MINERAL METABOLISM DURING THERAPY FOR HYPER- AND HYPOTHYROIDISM

The effects of thyroid hormones on various organs and metabolic systems have been the focus of intensive research. In this study we investigated the mechanisms of the changes in some parameters of bone and mineral metabolism before and during treatment of hyper- and hypothyroidism. Our study groups were as follows; 1) Untreated hyperthyroid patients (n = 38), 2) Hyperthyroid patients treated for three months (n = 21), 3) Untreated hypothyroid patients (n = 27), 4) Hypothyroid patients treated for three months (n = 20), and 5) Euthyroid control subjects (age, weight, sex and menopausal status matched) (n = 47). As expected, the mean serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and urinary Ca/creatinine and deoxypyridinoline (D-Pyr)/creatinine levels were higher in group-1 than in the control group. Serum PTH level was lower in group-1 than in group-5. However, after treatment for three months (group-2) we found that the serum and urinary levels of these parameters (except ALP) were not different than in the control group. Group-3 and group-4 did not show any differences in these parameters compared with group-5. Covariance analysis showed that urinary D-Pyr excretion had a positive, independent relationship to the serum free T3 level and age (P < 0.001 and P = 0.02, respectively). These results suggest that both bone formation and resorption markers increase in hyperthyroid patients, and with the treatment, particularly, in the period of first three months the bone resorption markers decrease rapidly. If the treatment is maintained the decrease slows, becoming more gradual. However, bone formation markers like ALP remain high in hyperthyroid patients during the treatment. In the light of this data, it is possible to conclude that osteoblastic activity lasts longer in hyperthyroidism. On the other hand, we demonstrated that these bone formation and resorption markers do not seem to be different in hypothyroid patients, even during the treatment, compared to the euthyroid controls.

Urotensin-II level and its association with oxidative stress in early diabetic nephropathy

OBJECTIVE Diabetic nephropathy is the most common cause of end stage renal failure. Early treatment of diabetic nephropathy depends on understanding the underlying mechanisms of the disease. In this study we investigated the role of U-II in early nephropathy and ıts association with oxidative stress, paraoxonase (PON)-1 and arylesterase. RESEARCH DESIGN AND METHODS Twenty-three diabetic patients with microalbuminuria, 23 diabetic patients with normoalbuminuria and 25 healthy individuals were enrolled in the study. Serum total antioxidant status (TAS), total oxidant status (TOS), PON-1, arylesterase, and urotensin-II (U-II) levels were measured. Oxidative stress index (OSI) percent ratio of TOS to TAS level was accepted as OSI. RESULTS Serum U-II levels were higher in the microalbuminuric diabetes group compared to the normoalbuminuric diabetic group and the healthy control group (p=0.009 and p=0.0001, respectively). Normoalbuminuric diabetic groups U-II levels were significantly higher compared to those of the healthy control group (p=0.0001). Correlation analysis yielded that plasma U-II levels are negatively correlated to TAS, arylesterase, and PON-1 levels (r=-0.395, p=0.001; r=-0.291, p=0.014; and r=-0.279, p=0.018, respectively) and that they had a positive correlation with OSI levels (r=0.312, p=0.008). These associations were confirmed in the multiple regression analysis. The results of multiple logistic regression analysis showed that oxidative stress is important in the development of microalbuminuria. CONCLUSION The data of this study reveal that increased serum U-II has a role in the development of diabetic nephropathy. This effect of U-II may be related to high levels oxidative stress parameters.

Eosinophilic myositis in calpainopathy: Could immunosuppression of the eosinophilic myositis alter the early natural course of the dystrophic disease?

An 11-year-old girl with a calpain-3 gene (CAPN-3) mutation and eosinophilic myositis on muscle biopsy had high serum CK levels and eosinophil counts which showed spontaneous fluctuations. After commencement of immunosuppressive therapy reciprocal changes occurred in response to alterations in doses of the medications. Subacutely evolving and spreading muscle weakness developed during tapering of the immunosuppressive medications. These observations suggest that either the occurrence of eosinophilic myositis or the withdrawal of the immunosuppressive treatment may have accelerated the clinical course of the calpainopathy in this case. The positive effect of immunosuppressive therapy might have implications for the management of calpainopathy with an inflammatory component.