Yakup Alicigüzel

Activities of xanthine oxidoreductase and antioxidant enzymes in different tissues of diabetic rats

Oxidative stress is an important pathogenic constituent in diabetic endothelial dysfunction. The aim of this study was to investigate whether an increase in oxidative stress related to xanthine oxidoreductase occurs in diabetes. Liver, brain, heart, and kidney xanthine oxidase (XO), xanthine dehydrogenase (XDH), antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase), and nitrite levels were measured in control and early and late diabetic rat models. Although diabetes had no impact on liver XO and XDH activity, XDH activity in heart, kidney, and brain was significantly greater in late diabetic rats than in controls. Selenium glutathione peroxidase (GPx) activity was found to be lower in the liver, brain, kidney, and heart of late diabetic rats than in controls. The measured decrease in selenium GPx activity was also observed in early diabetic heart, kidney, and brain. No significant change was observed in liver, brain, and kidney copper/zinc superoxide dismutase (Cu/Zn SOD) activity in early and late diabetic rat models compared with that in controls, whereas heart Cu/Zn SOD activity was significantly decreased in both early and late diabetic rats. Liver and brain catalase activity remained similar among the different experimental groups, whereas increased heart and kidney catalase activity was observed in both early and late diabetic rats. Liver, kidney, and brain nitrite levels were found to be increased in early diabetic rat models compared with those in controls. These data suggest that the increased XDH and decreased selenium GPx activity observed in the later stages of diabetes leads to enhanced oxidative stress in the heart, kidney, and brain, resulting in secondary organ damage associated with the disease.

Erythrocyte, plasma, and serum antioxidant activities in untreated toxic multinodular goiter patients

Erythrocyte, plasma, and serum antioxidant activities were studied in patients with newly diagnosed and untreated toxic multinodular hyperthyroid goiter and compared to healthy control subjects. Erythrocyte antioxidant enzyme activities, glutathione, malondialdehyde, and ceruloplasmin levels were significantly increased, whereas serum vitamin E, plasma vitamin C, and selenium levels were decreased in hyperthyroid patients compared to control subjects. The findings show that untreated toxic multinodular goiter causes profound alterations in components of the antioxidant system in erythrocytes indicative of increased oxidative stress. Taken together, these data suggest that hyperthyroid patients may benefit from dietary supplements of antioxidants.

Retinoic acid isomers protect hippocampal neurons from amyloid-β induced neurodegeneration

Attenuating amyloid-β mediated neurodegeneration is of major therapeutic consideration in the potential treatment of Alzheimer disease. Previously, we found that a high dietary consumption of retinoic acid was associated with a reduced incidence of Alzheimer disease. Therefore, in this study, we investigated whether amyloid-β mediated cell death in primary hippocampal neurons could be prevented by retinoic acid isomers. Our results suggest that retinoic acid isomers, including all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid, may play an important role in protecting neurons from amyloid-β-induced cell death. Retinoic acid may therefore afford a novel therapeutic mechanism for the treatment and prevention of Alzheimer disease.

Effects of Propylthiouracil Treatment on Antioxidant Activities in Blood of Toxic Multinodular Goiter Patients

Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.

THE EFFECT OF LIPOIC ACID ON LIPID PEROXIDATION AND VISUAL EVOKED POTENTIALS (VEPS) IN RATS EXPOSED TO CHRONIC RESTRAINT STRESS

The purpose of the present study was to investigate the effect of lipoic acid on lipid peroxidation, nitric oxide production, and visual evoked potentials (VEPs) in rats exposed to chronic restraint stress and to examine whether lipoic acid could prevent VEP alterations that occurred in stress together with lipid peroxidation. Forty male wistar rats, aged three months, were used in the present study. They were equally divided into four groups: control (C), the group treated with lipoic acid (L), the group exposed to restraint stress (S), and the group exposed to stress and treated with lipoic acid (LS). Chronic restraint stress was applied for 21 days (1 h/day) and lipoic acid (100 mg/kg/day) was injected intraperitonally to the L and LS groups for the same period. Brain and retina TBARS levels were significantly increased in the S group compared with the C group. Lipoic acid reduced retina and brain TBARS levels in the L and LS groups compared with their corresponding control groups. Restraint stress significantly increased nitrite and nitrate levels in both brain and retina in the stress group with respect to the control group. Lipoic acid produced a significant decrease in brain and retina nitrite and nitrate levels of the L and LS groups comparing with their corresponding control groups. All latencies of VEP components were prolonged in the S group with respect to the C group. The study found significant correlations between VEPs latencies and TBARS and nitrite and nitrate levels of retina and brain. Lipoic acid decreased the latencies of all VEP components in the LS group whereas it did not affect them in the L group with respect to their control groups. In summary, lipoic acid treatment was found effective in preventing VEP and TBARS alterations caused by stress.

N-Acetyl cysteine, L-cysteine, and β-mercaptoethanol augment seleniumglutathione peroxidase activity in glucose-6-phosphate dehydrogenasedeficient human erythrocytes

Abstract.In glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes, failure to maintain normal levels of reduced glutathione (GSH) due to decreased NADPH regeneration in the hexose monophosphate pathway results in acute hemolytic anemia following exposure to oxidative insults, such as ingestion of Vicia fava beans or use of certain drugs. GSH is a source of protection against oxidative attack, used by the selenium-dependent glutathione peroxidase (Se-GSH-Px)/reductase (GR) system to detoxify hydrogen peroxide and organic peroxides, provided that sufficient GSH is made available. In this study, Se-GSH-Px activity was analyzed in G6PD-deficient patients in the presence of reducing agents such as N-Acetyl cysteine, L-cysteine, and β-mercaptoethanol. Se-GSH-Px activity was decreased in G6PD-deficient red blood cells (RBCs). N-Acetyl cysteine, L-cysteine, and β-mercaptoethanol increased Se-GSH-Px activity in G6PD-deficient human erythrocytes, indicating that other reducing agents can be utilized to complement Se-GSH-Px activity in G6PD deficiency. Based on the increased susceptibility of G6PD-deficient patients to oxidative stress, the reported increase in Se- GSH-Px activity can facilitate the detoxification of reactive oxygen species.

Effect of the herbicide 4-CPA on human erythrocyte antioxidant enzymes in vitro.

Abstract To investigate the possible role of oxygen free radicals and oxidant stress in the toxic effects of phenoxyherbicides, we studied the in vitro effect of 4-chlorophenoxyacetic acid (4-CPA) on various human erythrocyte antioxidant enzymes, namely glucose-6-phosphate dehydrogenase, catalase, selenium-dependent glutathione peroxidase, glutathione reductase and Cu/Zn-superoxide dismutase. 4- CPA added in a dose of 1 ppm to human erythrocytes for 1 h caused a significant reduction in glucose-6- phosphate dehydrogenase (P <0.001) and catalase (P <0.001) activities, but did not significantly affect the activities of other enzymes. Such selective inactivation of specific erythrocyte antioxidant enzymes may play a role in the toxic effects of phenoxyherbicides.

CERULOPLASMIN AND VITAMIN E LEVELS IN TOXIC MULTINODULAR GOITER

The effect of the enhanced metabolic rate over antioxidant status was investigated in hyperthyroid individuals. Serum total T3 and T4 levels were measured by radioimmunoassay in 45 patients and 25 controls. The serum vitamin E was assayed fluorometrically in the hexane extract of serum. Serum ceruloplasmin activity was measured spectrophotometrically. Statistical significance was asessed by correlation regression analysis and paired t-test. The serum vitamin E levels decreased significantly as the levels of the thyroid hormones increased. For ceruloplasmin the opposite changes were observed: mean serum ceruloplasmin of hyperthyroid patients was greater than that of control group. Although the changes in vitamin E and ceruloplasmin concentrations did correlate with the levels of thyroid hormones in hyperthyroid patients, we observed no associations between these parameters in the euthyroid state. As these two parameters are the measure of oxidation potential, it may be suggested that raised free radical activity in hyperthyroidism cause the increased oxidative stress and increased general radical scavenging. The present data may indicate a direct effect of thyroid hormones on vitamin E and ceruloplasmin metabolism.

Effect of cadmium on antioxidant status in alloxane-induced diabetic rats.

Fifty-two healthy Swiss Male Albino rats aged two mo were used in this study. They were divided into four groups: control (C), diabetic (D), cadmium (Cd), and diabetic+Cd (D+Cd) groups. Diabetic condition was induced in D and D+Cd groups by administration of alloxane (5 mg/100 g). After this treatment, CD and D+Cd groups were injected with CdCl2 ip (2 mg/kg/wk). At the end of the 2-mo experimental period, thiobarbituric acid reactive substances (TBARS), plasma and erythrocyte selenium (SE), plasma ceruloplasmin (Cp), and vitamin E (vit E) were determined in four groups of rats.The erythrocyte Se was lower in the experimental groups than in the controls. Plasma Se was significantly decreased in the D and D+Cd groups compared with the control group. Plasma Cp was unaltered. Plasma vit E was significantly decreased in Cd group in comparison with the C, D, and D+Cd groups.

Myeloperoxidase, xanthine oxidase and superoxide dismutase in the gastric mucosa of helicobacter pylori positive and negative pediatric patients

The aim of this study was determination and comparison of the levels of myeloperoxidase (MPO), xanthine oxidase (XO), and superoxide dismutase (SOD) in gastric mucosa of children who were infected and noninfected with Helicobacter pylori (HP). The MPO, and XO enzyme activities were detected via kinetic measurement, and the MPO, XO and SOD enzyme protein levels were detected via Western blot, in antral mucosa specimens of 43 patients who underwent upper gastrointestinal endoscopy with various indications. The diagnosis of HP infection was made with a positive rapid urease test and histopathologic detection. MPO activity and enzyme protein levels were measured in 14 [8 HP (+) and 6 HP (−)], and in 9 [5 HP (+) and 4 HP (−)] while XO activity and enzyme protein levels were measured in 16 [10 HP (+) and 6 HP (−)] and in 9 [5 HP (+) and 4 HP (−)] patients, respectively. SOD protein level was detected in 13 [7 HP (+) and 6 HP (−)] patients. Of 43 patients 25 were HP (+) and 18 were HP (−). MPO activities were 75.6 ± 40.5 and 98.8 ± 44.1 U/g. protein (p = 0.302) while XO activities were 0.5 ± 0.3 and 0.4 ± 0.2 U/g. protein in HP (+) and HP (−) patients, respectively (p = 0.625). Measured enzyme protein levels of MPO, XO and SOD were found statistically indifferent in HP (+) and HP (−) patients (p = 0.327, p = 0.086, and p = 0.775, respectively). The results of this study revealed that, MPO, XO and SOD conditions in gastric mucosa alone were not affected from HP presence. Thats why MPO, XO, and SOD may not have important roles in the pathogenesis of HP related gastric disease in children.