Ahmet Sayal

Oxidative stress and nitric oxide related parameters in type II diabetes mellitus: effects of glycemic control

OBJECTIVES The aim of this study is to investigate the status of oxidative stress and nitric oxide related parameters in type II diabetes mellitus (DM) patients in which heart disease, atherosclerosis, retinopathy, and nephropathy commonly occur, and also to determine the effect of glycemic control on these parameters. DESIGN AND METHODS Erythrocyte copper zinc-superoxide dismutase (CuZn-SOD), erythrocyte and plasma selenium dependent glutathione peroxidase (Se-GPx), erythrocyte catalase (CAT) activities, erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels; nitrite/nitrate (NO(2)(-)/NO(3)(-)), cyclic guanosine monophosphate (cGMP) and nitrotyrosine levels in plasma of type II DM patients were measured. RESULTS Erythrocyte CuZn-SOD activities in type II DM were significantly higher than those of the control subjects (p < 0.05). TBARS levels in type II DM were significantly higher than the control subjects (p < 0.001). Plasma NO(2)(-)/NO(3)(-) levels in type II DM patients both during poor glycemic control and after three months of oral antidiabetic treatment were significantly higher than those of the control subjects (p < 0.001). Plasma cGMP levels in type II DM patients during poor glycemic control were significantly lower than those of control subjects (p < 0.001). CONCLUSION These results indicate that oxidative status and nitric oxide metabolism are affected in type II DM patients. We found high CuZn-SOD activity in type II DM patients. This increased activity could not protect the patients against the reactive oxygen species (ROS), since lipid peroxidation (defined by erythrocyte and plasma TBARS levels) still occurs in DM patients. After the therapy with oral antidiabetic agents for three months, erythrocyte SE-GPx and CAT activities were found to be decreased below the control values. Our results suggested that the low cGMP levels in the study may be a good marker of endothelium dysfunction in DM.

Increased oxidative stress and hypozincemia in male obesity

OBJECTIVES Antioxidants protect an organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Alterations in the levels of antioxidants and several essential trace elements in the plasma and various tissues of ob/ob mice have been reported previously. The aim of this study was to investigate oxidative status and trace elements in obese individuals. DESIGN AND METHODS Seventy-six obese men (body mass index (BMI) > 30 kg/m(2)) and 24 healthy, age-matched male control volunteers were enrolled in the study. Fasting plasma insulin, glucose, triglyceride (TG), total cholesterol, VLDL, and HDL levels, erythrocyte glutathione peroxidase (GSH-Px) and copper zinc-superoxide dismutase (CuZn-SOD) activities, and erythrocyte thiobarbituric acid reactive substances (TBARS) levels were measured in both groups. Erythrocyte copper (Cu), zinc (Zn) and iron (Fe) levels were also measured. RESULTS We found that the mean Cu and Fe levels in obese individuals were not significantly different than those in the control group, whereas the mean Zn levels were significantly lower than those of the control group (p = 0.023). The mean erythrocyte CuZn-SOD and GSH-Px levels in obese individuals were significantly lower than those in controls (p = 0.001) whereas erythrocyte TBARS levels were significantly higher (p = 0.001) than those of the control group. CONCLUSION We conclude that male obesity is associated with defective antioxidant status and hypozincemia, which may have implications in the development of obesity related health problems.

Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease

OBJECTIVES In this study we aimed to determine the levels of Glutathione peroxidase (GSH-Px) and Malondialdehyde (MDA) in patients with inflammatory bowel disease (IBD) to investigate their contribution to tissue injury in inflammatory bowel disease. DESIGN AND METHODS Forty-seven GSH-Px patients (35 with ulcerative colitis and 12 with Crohns disease) and 30 healthy controls were included in the study. Their plasma and MDA levels were compared using nonparametric statistical methods. RESULTS Plasma GSH-Px levels of the patients group were significantly higher than the control group (p < 0.001). There was no significant difference between patients and controls in view of plasma levels of MDA. CONCLUSIONS High levels of GSH-Px, which is response against oxidative stress, indicates the increase of free radicals in IBD, while normal plasma MDA levels suggest the clearance of free radicals without leading to lipid peroxidation. Our result reveals that there is an existing antioxidant capacity despite oxidative stress in patients with IBD.

Plasma Trace Element, Plasma Glutathione Peroxidase, and Superoxide Dismutase Levels in Epileptic Children Receiving Antiepileptic Drug Therapy

Summary: Some antiepileptic drugs (AEDs) may altertrace element metabolism and free radical scavenging enzyme activities in humans and experimental animals. We investigated the effect of longterm AED therapy on copper (Cu), zinc (Zn), manganese (Mn), selenium (Se), magnesium (Mg), glutathione peroxidase (GSH‐PX), and superoxide dismutase (SOD) in the plasma in children with epilepsy. During treatment with valproate (VPA) or carbamazepine (CBZ) monotherapy plasma Cu, Zn, Mn, Se, and Mg concentrations of patients were not statistically different from those of control subjects. The level of seoxidation may be causally involved in some forms of epilepsies, and the decreased free radical scavenging enzyme activity is believed to cause the increased risk of anidiosyncratic drug reaction encountered in the manage‐ment of epilepsy. Because GSH‐PX and SOD are themost important members of antioxidant defense mechanisms, we quantitated the activities of these enzymes inplasma of children with epilepsy receiving VPA or CBZ. Only plasma GSH‐PX activities in VPA group werehigher than those of the control group, and the differencewas statistically significant.

Effects of Statins on Oxidative Stress

Free oxygen radicals and insufficient antioxidant enzymes have been implicated in the pathogenesis of hypercholesterolemia (HC). Trace elements function as cofactors in antioxidant enzymes. Antioxidant system and trace elements were investigated in many different studies including HC, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in hypercholesterolemic patients given fluvastatin therapy.We examined malondialdehyde (MDA), copper zinc-superoxide dismutase (CuZn-SOD), and glutathione peroxidase (GSH-Px) activities together with copper (Cu), iron (Fe), and zinc (Zn) levels in erythrocytes of 35 patients with HC and 27 healthy control subjects. It was found that in patients with HC, erythrocyte MDA was significantly higher than those of controls and erythrocyte CuZn-SOD and GSH-Px activities were significantly lower in patients with HC. Erythrocyte iron levels were significantly higher than those of controls, and erythrocyte copper and zinc levels were significantly lower in patients with HC. Plasma lipid levels and the oxidative state were analyzed in statin-treatment groups given fluvastatin therapy before and after a 3-mo treatment period.In conclusion, we found that fluvastatin has significant antioxidant properties and these effects might be very important in managing dyslipidemia by improving endothelial function.

Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata

Alopecia areata (AA) is an autoimmune inflammatory disease. However, little is known about the alterations in lipid peroxidation and antioxidant enzymes in the scalp of patients with AA. Therefore, the aim of this study was to investigate the status of oxidative stress in the scalp of patients with AA. We measured the levels of thiobarbituric acid reactive substances (TBARS) as lipid peroxidation status, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as antioxidant enzymes in the scalp of ten patients with AA and ten control subjects. The levels of TBARS in scalp of patients with AA (3654.1+/-621.2 nmol/g tissue) were significantly higher than those of controls (1210.2+/-188.8 nmol/g tissue) (P=0.002). The levels of SOD (134.8+/-23.8 U/g tissue) and GSH-Px (332.7+/-66.2 U/g tissue) in scalp of patients with AA were also significantly higher than those of controls (63.2+/-8.8 U/g tissue, 112.0+/-18.4 U/g tissue, respectively) (P=0.019, P=0.002, respectively). The mean levels of TBARS, SOD and GSH-Px in early phase of disease were increased 2-fold as compared with late phase of the disease. These results indicate that oxidative status is affected in AA. Lipid peroxidation and antioxidant enzymes may be involved in the pathogenesis of AA. Furthermore, we found high SOD and GSH-Px activities in the scalp of patient with AA. These high levels could not protect the patients against the reactive oxygen species, because lipid peroxidation could not be lowered in AA patients.

The antioxidant effect of β-Glucan on oxidative stress status in experimental spinal cord injury in rats

This study was performed to investigate the antioxidant effect of β-Glucan in experimental spinal cord injury (SCI). Injury was produced using weight-drop technique in rats. β-Glucan was given by intraperitoneal injection following trauma. The rats were sacrificed at the sixth day of injury. Oxidative stress status was assessed by measuring the spinal cord tissue content of Malonyldialdehyde (MDA), Superoxide Dismutase (SOD) and Gluthatione Peroxidase (GSH-Px) activities. No effect of β-Glucan on SOD and MDA activities was found but, GSH-Px levels were found to decrease to the baseline (preinjury) levels when it was compared to untreated group (U=0.000; p=0.002). According to our results, β-Glucan works like a scavenger and has an antioxidant effect on lipid peroxidation in spinal cord injury.

Manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with risk of early‐onset prostate cancer

Prostate cancer continues to be the most frequently diagnosed neoplasm, and the second leading cause of cancer‐related mortality in men. Oxidative stress may enhance prostatic carcinogenesis. Manganese superoxide dismutase (MnSOD) is the only known superoxide scavenger in mitochondria. It plays a key role in antioxidant defense as mitochondria are important for oxidative metabolism coupled to the electron transport chain and oxidative phosphorylation and hence, ROS production. A T→C single nucleotide substitution, resulting in a Val→Ala change at position 9 (Ala‐9Val), which alters the secondary structure of the protein, has been noted to affect transport of MnSOD into the mitochondria. We have determined the MnSOD genotype in 85 prostate cancer cases and 151 control subjects. Ala‐9Val polymorphism was determined using real time polymerase chain reaction (PCR) amplification with fluorescently labeled primers. No significant difference was found in prostate cancer susceptibility in the subjects with Ala/Ala and Val/Ala genotype compared with Val/Val genotype (Odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.69–2.42; p = 0.416). We did not observe an association of the MnSOD genotype or allele frequency between subgroups of cases divided by disease status (aggressive vs. non‐aggressive prostate cancer). However, in the analyses stratified by the age at diagnosis we have observed that men homozygous for Ala had a 5.2‐fold increased risk of early‐onset prostate cancer (under age of 65) compared to men homozygous for Val allele (p = 0.05). These data suggest that Ala/Ala MnSOD genotype in the Macedonian population could have an influence on early onset of prostate cancer, but no impact on the subsequent development of the disease. Copyright

Effect of volatile anesthetics on oxidative stress due to occupational exposure.

Possible health hazards from long-term exposure to inhalation anesthetics cannot yet be definitively excluded. One of the adverse effects of general anesthetics is the exogen sources of reactive oxygen radicals that are responsible for several diseases. We designed the present study to determine the effect of volatile anesthetics on oxidative stress due to occupational exposure. We enrolled 30 anesthesia and surgery personnel who had been exposed to inhalation anesthetics for 3 years and 30 healthy volunteer personnel who had not been exposed to inhalation anesthetics at any period of their life as the control group. Blood samples were taken from both groups for determination of superoxide dismutase, glutathione peroxidase, and their cofactors, which are selenium, copper, and zinc levels. Our results revealed that plasma and erythrocyte antioxidant activity and trace element levels were significantly lower in operating room personnel compared to that in the control groups. We concluded that the antioxidant defense system was affected by free radical injury in anesthesia and surgery personnel who had been exposed to inhalation anesthetics chronically. Therefore, minimizing occupational exposure to volatile anesthetics is important for protecting operation room personnel from hazards. Operating room personnel should also take antioxidant supplements.

Trace elements and antioxidant enzymes in Behçet's disease.

Abstract. Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of Behçets disease (BD). Trace elements function as cofactors to antioxidant enzymes. The antioxidant system and trace elements were investigated in many different studies, including BD, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in BD to contribute to the knowledge of pathogenesis and treatment of this disease. We examined glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities together with selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels in plasma and erythrocytes of 50 patients with BD and 30 healthy controls. It was found that in patients with BD, erythrocyte GSH-Px and SOD activities and erythrocyte Se, plasma Fe, Mn, and Zn levels were significantly lower than those of controls and that plasma Cu, erythrocyte Zn, and Mn levels were significantly higher in patients with BD. Insufficient antioxidant enzyme activities were observed in patients with BD. The mechanism(s) of this phenomenon is not clear. Therefore, supplementation with trace elements involved in the antioxidative processes may increase scavenger enzyme activities, and consequently, an improvement in clinical symptoms may be expected.