Huseyin Vural

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.

Plasma manganese, selenium, zinc, copper, and iron concentrations in patients with schizophrenia.

A number of essential trace elements play a major role in various metabolic pathways. Selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) are essential trace elements that have been studied in many diseases, including autoimmune, neurological, and psychiatric disorders. However, the findings of previous research on the status of trace elements in patients with schizophrenia have been controversial. We studied these elements in patients with a DSM-IV diagnosis of schizophrenia and compared them with sex- and age-matched healthy controls. Plasma Cu concentrations were significantly higher (p<0.01) and Mn and Fe concentrations were lower (p<0.05 and p<0.05, respectively) in schizophrenic patients than in controls. Se and Zn concentrations and protein levels did not differ between patients and healthy controls. These observations suggest that alterations in essential trace elements Mn, Cu, and Fe may play a role in the pathogenesis of schizophrenia. However, findings from trace element levels in schizophrenia show a variety of results that are difficult to interpret.

Is the Arginine-Nitric Oxide Pathway Involved in the Pathogenesis of Schizophrenia?

The reciprocal regulation of arginase and nitric oxide synthase (NOS) in L-arginine-metabolizing pathways has been demonstrated. There are various evidences of the role of the nitric oxide (NO) in several neuropsychiatric disorders including schizophrenia. However, there is no study which has investigated the role of arginase as an important part of the arginine regulatory system affecting NOS activity in schizophrenia. This study aims to investigate arginase, manganese (Mn) and total nitrite levels (a metabolite of NO) and their relationship to the arginine-NO pathway in patients with schizophrenia. Arginase activities, Mn and total nitrite levels were measured in plasma from 46 patients with schizophrenia and 32 healthy control subjects. Plasma arginase activities and Mn were found to be significantly lower and total nitrite level higher in patients with schizophrenia compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of schizophrenia.

The role of oxidative stress in diabetic retinopathy

Purpose To investigate the role of oxidative stress in the development of diabetic retinopathy.Methods This study included 25 patients with diabetic retinopathy (group 1), 34 patients with non-insulin-dependent diabetes mellitus without any angiopathy complications (group II) and 26 healthy subjects (group III). The serum malondialdehyde (MDA)-like metabolite levels as an index of lipid peroxidation, the erythrocyte glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and serum vitamin C levels of the patients and healthy subjects were measured.Results The mean serum concentration of MDA-like metabolites of patients in group I was 4.38 ± 1.31 nmol/ml, in group II was 3.38 ± 0.95 nmol/ml and in group III was 2.61 ± 0.85 nmol/ml. There were significant differences between the groups (p = 0.001 for group I compared with group II, p = 0.0001 for group I compared with group III and p = 0.002 for group II compared with group III). There was a significant correlation between the serum lipid peroxidation concentrations and duration of the disease (r = 0.36, p = 0.047). The mean erythrocyte GSH-Px and SOD levels of group I were respectively 68.97 ± 18.04 and 1597.78 ± 296.46 U/g Hb, of group II were 64.30 ±19.26 and 1581.33 ± 278.08 U/g Hb, and of group III were 65.52 ± 17.58 and 1587.44 ± 281.17 U/g Hb. There were no significant differences among the antioxidant enzyme levels in the three groups (p > 0.05). The mean serum vitamin C level in group I was 42.72 ± 8.90 μmol/l, in group II was 49.26 ± 11.52 μmol/l and in group III was 58.57 ± 9.75 μmol/l. There were significant differences among the mean serum vitamin C levels of the three groups (p = 0.02 for group I versus group II p = 0.001 for group I versus group III and p = 0.002 for group II versus group III).Conclusions Free radicals forming in diabetes mellitus and increasing over time may play a role in the development of diabetic retinopathy, which is an important complication of the disease.

Oxidative stress of platelets and thrombocytopenia in patients with vivax malaria

Oxidative stress and antioxidative capacity of platelets and the relationship with thrombocytopenia were determined in patients with vivax malaria and compared with those of healthy subjects. Whole blood thrombocyte count, platelet superoxide dismutase and glutathione peroxidase activities of patients with vivax malaria were lower and platelet lipid peroxidation levels were higher in patients than those of healthy subjects. There was an important negative correlation between whole blood thrombocyte count and platelet lipid peroxidation level. The antioxidative mechanisms of thrombocytes were insufficient in malaria patients and caused oxidative stress. The oxidative damage of thrombocytes might be important in the ethiopathogenesis of thrombocytopenia occurring in malaria.

The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder

Abstract.There is a reciprocal regulation of arginase and nitric oxide synthase (NOS) in L-arginine-metabolizing pathways. Nitric oxide (NO) may be involved in some psychiatric disorders like schizophrenia, depression and bipolar affective disorder (BPAD). To our knowledge, there is no study in the literature in which the role of arginase, an important part of the arginine regulatory system affecting NOS activity, was investigated in BPAD. This study aims to investigate arginase, manganese (Mn) and total nitrite levels (a metabolite of NO) and their relationship to the arginine-NO pathway in patients with BPAD. Arginase activities, Mn and total nitrite levels were measured in plasma from forty-three patients with BPAD (Type one) and thirty-one healthy control subjects. Plasma arginase activities and Mn were found to be significantly lower and total nitrite level higher in patients with BPAD compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of BPAD.

Altered anti-oxidant status and increased lipid peroxidation in marasmic children.

Abstract Background: Protein energy malnutrition (PEM) is a common pediatric health problem in developing countries. Although the clinical features of PEM are well known, its pathophysiology is still unclear. Free radicals have been implicated in pathogenesis of PEM. In the present study, oxidant/anti‐oxidant status in marasmus was investigated.

The effect of melatonin on bleomycin-induced pulmonary fibrosis in rats

The present investigation was designed to determine the protective effects of melatonin against bleomycin (BLM)‐induced oxidant lung toxicity. Wistar‐albino rats were divided into four groups: saline (SA, 0.4 mL/animal), 1% ethanol‐saline (ALC, 0.4 mL/animal), bleomycin sulphate (BLM, 10 mg/kg), or bleomycin sulphate + melatonin (BLM, 10 mg/kg + MLT, 10 mg/kg). All injections were given intraperitoneally (i.p.), twice weekly for a period of 3 wk (a total of seven injections for each group). Twenty‐five days after BLM treatment, pulmonary fibrosis was assessed as hydroxyproline content in lung homogenates. Findings show that BLM‐induced pulmonary injury resulted in increases in bronchoalveolar lavage fluid (BALF) biomarkers including total protein, lactate dehydrogenase (LDH), glutathione‐peroxidase (GSH‐Px), superoxide dismutase (SOD), and catalase (CAT). Additionally, the levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation (LPO), were also increased in BALF. Conversely, the level of glutathione (GSH) was reduced in BALF of BLM‐treated rats. Melatonin provided protection against BLM‐induced pulmonary fibrosis by suppressing oxidative stress. It abolished BLM‐stimulated LPO and reversed the imbalance between oxidants and antioxidants in the BALFs. Results thus indicate that melatonin inhibits BLM‐induced lung toxicity associated with oxidative damage.

Increase of free oxygen radicals in aqueous humour induced by selective Nd:YAG laser trabeculoplasty in the rabbit

Purpose To investigate the impact of selective Nd:YAG laser trabeculoplasty on free oxygen radicals and antioxidant enzymes of the aqueous humour in the rabbit. Methods One eye of 18 rabbits was subjected to 360° selective laser trabeculoplasty (LT) with a frequency-doubled Nd:YAG laser (532 nm). The anterior chamber aqueous humour was aspirated 3, 12 hours and 1, 3, 7, 10 days after treatment. Lipid peroxide (LPO) and glutathione S transferase (GST) levels and superoxide dismutase (SOD) activities of aqueous humour were measured. Results Concentrations of LPO in the aqueous humour of the treated eyes were significantly higher than the untreated eyes until the 7th day. Aqueous SOD activity significantly decreased 3 hours after LT and remained low until day 7. Aqueous GST levels were significantly decreased between 12 hours and 7 days after the LT. Conclusions Selective LT was followed by an immediate increase in the aqueous humour LPO concentration and decreases of SOD and GST in the rabbit, probably due to photo-vaporization and photodisruption caused by the frequency- doubled Nd:YAG laser. The increased aqueous LPO levels suggest that free oxygen radicals are formed in the pigmented trabecular meshwork during LT, and may be responsible for the inflammatory complications of this procedure.