Nilgün Altan

A quantitative evaluation of total antioxidant status and oxidative stress markers in preeclampsia and gestational diabetic patients in 24–36 weeks of gestation

OBJECTIVE To assess the plasma and serum maternal total antioxidant status, circulating levels of lipid peroxidation breakdown products (MDA), protein oxidation markers (AOPPs), myeloperoxidase (MPO) and lipid hydroperoxide (LHP) in preeclampsia, gestational diabetes mellitus (GDM) patients and compare them with noncomplicated normal pregnancies between 24 and 36 weeks of gestation. STUDY DESIGN 27 GDM, 27 preeclampsia and 29 noncomplicated singleton pregnancies were included. The blood samples were taken at the diagnosis of disease. RESULTS TAS was decreased in GDM and preeclampsia when compared to normal pregnancies. MDA levels were higher only in GDM group than normal pregnancies. AOPP levels were increased but MPO and LHP levels were not changed both in GDM and preeclampsia when compared to normal pregnancies. CONCLUSIONS We concluded that increased oxidative stress and reduction in antioxidant defense mechanisms may contribute to disease processes both in GDM and preeclampsia.

Effect of the Sulphonylurea Glibenclamide on Liver and Kidney Antioxidant Enzymes in Streptozocin-Induced Diabetic Rats

AbstractBackground: Alterations in catalase (CAT) and superoxide dismutase (SOD) activity have been reported in diabetes mellitus. Glibenclamide (glyburide), a member of the second-generation sulphonylureas, provides effective treatment for patients with moderate diabetes. The action of the liver plays an important role in its glucose-lowering effect, suggesting that glibenclamide also exerts a direct effect on liver enzyme activities. Objective: To evaluate the effect of glibenclamide on the activities of antioxidant enzymes (CAT and SOD) in liver and kidney tissue of diabetic rats. Methods: Thirty-nine rats were included in this study. Moderate diabetes mellitus was induced with streptozocin (freshly dissolved in citrate buffer, ph 4.5) 55 mg/ kg in 22 rats. Eight of these diabetic rats were left untreated, insulin was administered to six diabetic rats, and glibenclamide was administered to eight rats with moderate diabetes. Liver and kidney CAT and SOD activities were measured in all rats. Results: Hepatic CAT and SOD activities were significantly reduced in diabetic animals (p < 0.05 for both activities). Glibenclamide treatment of diabetic rats for 5 weeks reversed the changes observed in diabetic liver tissues (p < 0.05). However, renal CAT and SOD activities were unchanged. In addition, high blood glucose levels of diabetic rats were decreased following glibenclamide treatment. Conclusion: Administration of glibenclamide to diabetic rats reversed diabetes-induced changes, suggesting that glibenclamide may directly increase liver CAT and SOD activity.

Thyroid hormones mediated effect of insulin on alloxan diabetic rat atria

1. The influence of alloxan-induced diabetes was studied on spontaneously beating rat atria. Diabetic atria were found to have decreased rates, increased contractility and decreased responsiveness to both inotropic and chronotropic effects of isoprenaline. 2. Thyroid hormone levels were significantly reduced in diabetic animals. This revealed that the decrease in atrial beta-adrenergic responses was associated with a reduction in serum levels of thyroid hormones. 3. Insulin treatment of diabetic rats for 10 days corrected the changes observed in diabetic atria. Serum levels of thyroid hormones returned to normal following insulin treatment as well. 4. Administration of insulin to thyroidectomized-diabetic rats did not reverse the diabetes-induced changes suggesting that thyroid hormones are needed for insulin to normalize the alterations observed in diabetic atria.

Oxidant/antioxidant balance in patients with thyroid cancer

PURPOSE To compare the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of lipid peroxidation product malondialdehyde (MDA) in blood samples of thyroid cancer patients compared to healthy controls. METHODS 43 control subjects (mean age 44+/-13 years) and 43 patients (43+/-13 years) presented with multinodular goiter whose fine needle aspiration revealed malignant cytology were included into this study. The SOD, MDA and GSH-Px activities were measured in control subjects, and before/20 days after thyroidectomy in thyroid cancer patients. RESULTS SOD activities of pre-thyroidectomy, post-thyroidectomy and control groups were not different (p>0.05). Before thyroidectomy GSH-Px activities were lower (p<0.05) and MDA levels were higher (p<0.05) than the control group. In post- thyroidectomy, GSH-Px activity (p<0.05) increased, and MDA levels (p<0.05) decreased compared to prethyroidectomy levels. After thyroidectomy GSH-Px activity was significantly higher than the control group (p<0.05). Although post-thyroidectomy MDA levels significantly decreased, they were still higher than the control group (p<0.05). CONCLUSION The superoxide dismutase does not seem to change with thyroid cancer and thyroidectomy but both antioxidant glutathione peroxidase and lipid peroxidation product malondialdehyde do. These preliminary findings may point out oxidant/antioxidant imbalance associated with thyroid cancer.

The effects of sulfonylurea glyburide on superoxide dismutase, catalase, and glutathione peroxidase activities in the brain tissue of streptozotocin-induced diabetic rat.

OBJECTIVES A member of the second-generation sulfonylureas, glyburide (GLY; glibenclamide) provides an effective therapy for patients with type 2 diabetes. It stimulates pancreatic insulin secretion, suggesting that it is effective in the treatment of type 2 diabetes primarily by elevating the circulating insulin levels. However, experimental evidences have indicated that sulfonylureas have also had an extrapancreatic effect, which may directly contribute toward maintaining blood glucose homeostasis during diabetes. METHODS In this study, we administrated GLY to streptozotocin-induced diabetic rats and determined the effects of such treatment on activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) from brain tissue. RESULTS AND DISCUSSION Brain CAT and GPx activities were not significantly different in the diabetic group compared to controls (P>.05), but the SOD activity was significantly reduced in the diabetic group compared to controls (P<.001). GLY treatment of 4 weeks had restored the SOD and CAT enzyme activities in diabetic rat brain (P<.05). In addition, high blood glucose levels of untreated diabetic rats were decreased following the GLY treatment (P<.01). Administration of GLY to diabetic rats restored the diabetes-induced changes, suggesting that GLY could restore the brain SOD and CAT activities.

The effect of radiofrequency radiation on DNA and lipid damage in female and male infant rabbits

Purpose: We aimed to design a prolonged radiofrequency (RF) radiation exposure and investigate in an animal model, possible bio-effects of RF radiation on the ongoing developmental stages of children from conception to childhood. Materials and methods: A total of 72 New Zealand female and male white rabbits aged one month were used. Females were exposed to RF radiation for 15 min/day during 7 days, whereas males were exposed to the same level of radiation for 15 min/day during 14 days. Thirty-six female and 36 male infant rabbits were randomly divided into four groups: Group I [Intrauterine (IU) exposure (−); Extrauterine (EU) exposure (−)]: Sham exposure which means rabbits were exposed to 1800 MHz Global System for Mobile Telecommunication (GSM)-like RF signals neither in the IU nor in the EU periods. Group II [IU exposure (−); EU exposure (+)]: Infant rabbits were exposed to 1800 MHz GSM-like RF signals when they reached one month of age. Group III [IU exposure (+); EU exposure (−)]: Infant rabbits were exposed to 1800 MHz GSM-like RF signals in the IU period (between 15th and 22nd days of the gestational period). Group IV [IU exposure (+); EU exposure (+)]: Infant rabbits were exposed to 1800 MHz GSM-like RF signals both in the IU period (between 15th and 22nd days of the gestational period) and in the EU period when they reached one month of age. Biochemical analysis for lipid peroxidation and DNA damage were carried out in the livers of all rabbits. Results: Lipid peroxidation levels in the liver tissues of female and male infant rabbits increased under RF radiation exposure. Liver 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels of female rabbits exposed to RF radiation were also found to increase when compared with the levels of non-exposed infants. However, there were no changes in liver 8-OHdG levels of male rabbits under RF exposure. Conclusion: Consequently, it can be concluded that GSM-like RF radiation may induce biochemical changes by increasing free radical attacks to structural biomolecules in the rabbit as an experimental animal model.

Erythrocyte Glutathione Levels in Lithium-Induced Hypothyroidism

AbstractBackground and objective: Lithium, widely used in the prophylaxis of psychiatric patients with bipolar affective disorders, is well known to induce thyroid alterations. However, a possible metabolic linkage between blood thyroxine levels and its regulatory function on erythrocyte glutathione concentration has not yet been evaluated in lithium-treated patients. The aim of this study was to assess the antioxidative capacity of erythrocytes in lithium-induced hypothyroidism before and after thyroxine replacement. Patients and methods: Thyroid ultrasound with clinical and laboratory evaluation of thyroid function and thyroid-stimulating hormone assay were performed prior to and at 6-month intervals during lithium prophylaxis in 76 patients with bipolar affective disorders. The daily lithium dosage was adjusted to 600–1200mg and the mean duration of treatment was 2.2 ± 0.4 years. Final assessment revealed that 12 patients had evidence of primary hypothyroidism, and these were assigned as the test group. Lithium prophylaxis was supplemented with thyroxine at a dosage of 100 mg/day within 6 months after thyroid dysfunction was diagnosed. Red blood cell superoxide dismutase activities and the glutathione contents were measured before and after thyroxine replacement. In order to assess the effect of long-term lithium administration on red blood cell glutathione and superoxide dismutase levels, 12 patients who had not developed hypothyroidism during the follow-up period were selected for the lithium-treated euthyroid group. Mann Whitney U-test and Wilcoxon rank sum W-test were used for comparison of data. Results: A comparison of the lithium-treated test group with healthy volunteers and their own values after thyroxine replacement revealed a significant decrease in red blood cell glutathione concentrations (p = 0.000) in the hypothyroid state. However, no clinically significant changes were observed in red blood cell superoxide dismutase activities of the test group. A statistical survey also demonstrated that there was no significant difference in the thyroid-stimulating hormone values as well as the red blood cell glutathione contents or superoxide dismutase activities between healthy controls and lithium-treated euthyroid subjects. Conclusions: It is most likely that lithium primarily inhibited hormone production in the thyroid and that this led to a compensatory increase in thyroid-stimulating hormone secretion with a significant decrease in the red blood cell glutathione content. While the red blood cell glutathione content of hypothyroid patients was reduced to 40% of the post-thyroxine level, unchanged superoxide dismutase activity might render the erythrocytes vulnerable to oxidative stress and ultimately haemolysis. Thyroxine replacement during lithium prophylaxis of psychiatric patients is advisable in order to prevent subclinical hypothyroidism and related defects of erythrocyte antioxidant capacity.

The relationship between erythrocyte superoxide dismutase activity and plasma levels of some trace elements (Al, Cu, Zn) of dialysis patients

1. The effect of erythropoietin and some trace elements on superoxide dismutase (SOD) activity of dialysis patients have been studied. 2. SOD activity of dialysis patients was found to be decreased. 3. The effect of erythropoietin on SOD activity was not found in vitro. 4. Plasma and erythrocyte aluminum increased in dialysis patients, but no significant change in plasma copper was found. 5. Plasma zinc levels of dialysis patients were found to be decreased. 6. These results suggest that inhibition of erythrocyte SOD activity of dialysis patients may contribute to their anemia.

Nitric oxide-mediated liver injury in the presence of experimental bile duct obstruction.

We investigated the possible mechanism of common bile duct (CBD) obstruction-related liver cell necrosis in a guinea pig model during a 24-hour period of biliary occlusion. A total of 30 male albino guinea pigs were randomly and equally assigned to two groups. Group 1 underwent sham laparotomy (SL), and group 2 underwent common bile duct ligation (CBDL). All the animals were followed for the first 24-hours after operation. The liver antioxidant defense was examined by measuring liver total superoxide dismutase (TSOD), copper/zinc-containing superoxide dismutase (Cu-ZnSOD), manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPx) activities as well as the reduced glutathione (GSH) concentration. Severity of necrosis was assessed by blind quantitation of liver specimens using a histologic scoring system. Histologic evidence of grade +2 hepatocellular necrosis was observed in the CBDL group, as was a more than fourfold increase in plasma nitrite plus nitrate [NOx] concentrations in these animals. Although no significant difference was found between the two groups for liver Cu-ZnSOD activity, the CBDL group showed a marked decrease in MnSOD activity. Concomitant increases in liver GPx activity and the GSH level were measured in the CBDL group. These data supported the hypothesis that excessive production of [NOx] and its derivative peroxynitrite contribute to a coexisting MnSOD deficiency in the mitochondria and lead to liver cell necrosis in cholestatic animals.

Effect of the sulfonylurea glyburide on superoxide dismutase activity in alloxan-induced diabetic rat hepatocytes

In the present study we administrated glyburide (glibenclamide) to type 2 (NIDDM) diabetic rats and determined the effect of such treatment on liver superoxide dismutase (SOD) activity. Hepatic SOD activity was significantly reduced in diabetic animals. Glyburide treatment of diabetic rats for 4 weeks corrected the changes observed in diabetic liver. In addition, blood glucose levels of untreated diabetic rats decreased following glyburide treatment. Administration of glyburide to diabetic rats reversed the diabetes-induced changes, suggesting that glyburide may directly increase liver SOD enzyme activity.