The effects of N-acetylcysteine and epigallocatechin-3-gallate on liver tissue protein oxidation and antioxidant enzyme levels after the exposure to radiofrequency radiation.

PURPOSE: The widespread and sustained use of mobile and cordless phones causes unprecedented increase of radiofrequency radiation (RFR). The aim of this experimental study was to investigate the effect of 900 MHz Global System for Mobile Communications (GSM)-modulated RFR (average whole body Specific Absorption Rate (SAR) of 0.4 W/kg, 10 or 20 min daily for consecutive 7 days) to the liver tissue of guinea pigs and the protective effects of antioxidant treatments. MATERIALS AND METHODS: Adult male guinea pigs were randomly divided into nine groups as: Group I (sham/saline), Group II (sham/EGCG), Group III (sham/NAC), Group IV (10-min RF-exposure/saline), Group V (20-min RF-exposure/saline), Group VI (10-min RF-exposure/EGCG), Group VII (20-min RF-exposure/EGCG), Group VIII (10-min RF-exposure/NAC), and Group IX (20-min RF-exposure/NAC). Protein oxidation (PCO), advanced oxidation protein products (AOPP) and antioxidant enzyme activities of superoxide dismutase (SOD) were evaluated after the exposure and the treatments with N-acetylcysteine (NAC) and (-)-epigallocatechin-3-gallate (EGCG). RESULTS AND CONCLUSIONS: Significant decreases in the activities of SOD were observed in the liver of guinea pigs after RFR exposure. Protein damage did not change due to RFR exposure. On the other hand, only NAC treatment induced increased PCO levels, whereas EGCG treatment alone elevated the level of AOPP. Due to antioxidants having pro-oxidant behavior, the well decided doses and treatment timetables of NAC and ECGC are needed.

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.

Genotoxicity assessment of carp (Cyprinus carpio L.) fingerlings by tissue DNA damage and micronucleus test, after environmental exposure to fenitrothion.

The purpose of this study was to evaluate the adverse effects of sublethal doses of fenitrothion, an organophosphothionate insecticide on brain, gill, liver, and muscle tissues as a ratio of 8-OHdG to dG to indicate the DNA damage and erythrocyte micronucleus frequency for genotoxicity of carp (Cyprinus carpio L.) fingerlings. In our study, the mean weights and lengths of the fish (n = 4-12) were 31.13 ± 14.24 g and 12.53 ± 1.41, respectively. Before the experiment, fish were maintained in aerated dechlorinated tap water at 21.8 ± 1 °C and fed daily with commercial feed at a rate of 2% of their body weights. Experiments were conducted under static conditions in the aquaria. Technical grade (95%) fenitrothion was diluted in acetone to give a dosing solution of 10 mg/L. The increased lesions/106 DNA bases (p < 0.05) of liver tissue of exposure group (0.49 ± 0.18) was observed when compared to control group (0.28 ± 0.30). There was not any significant differences between brain tissues, no damage were detectable in gill and muscle tissues of control groups, and in exposure groups altered levels of damage were detected for gill (0.06 ± 0.05) and muscle (0.16 ± 0.21) tissues. The increased micronucleus frequencies (%) in erythrocytes of carp following the exposure to 48 h fenitrothion (6.43 ± 3.89; p<0.05) was observed when compared to control group (1.29 ± 1.03). The available data indicate that there is still lack of well-established dose-response relationships between occupational or environmental exposures and the induction of 8-OHdG. Such biomarkers may be used in assessing adverse/toxic effects of pesticides as environmental stressors.

Oxidative DNA damage: the thyroid hormone-mediated effects of insulin on liver tissue.

Thyroid hormone affects glucose homeostasis with its actions between the skeletal muscle and liver and the altered oxidative and non-oxidative glucose metabolism. In our study three chemicals are considered biomarkers associated with oxidative stress for protein modifications were measured; 8-hydroxy-2-deoxyyguanosine (8-OHdG), a major lesion that can be generated by reactive oxygen species for DNA damage, protein carbonyl content (PCO), products of protein oxidation and advanced oxidation protein products (AOPPs) a dithyrosine containing cross-linked protein products. The purpose of the recent study was to determine the effects of insulin and T4 or their combination in diabetic, thyroidectomized, or diabetic-thyroidectomized rats and possible relations with oxidative DNA and protein damages. For this purpose, rats were assigned to eight groups: Group 1; control, Group 2; diabetes, Group 3; diabetes+insulin, Group 4; surgically thyroidectomized control, Group 5; thyroidectomized+diabetes, Group 6; thyroidectomized+diabetes+insulin, Group 7; thyroidectomized+diabetes+insulin+thyroid hormone, levothyroxin sodium, 2.5 µg/kg and Group 8; thyroidectomized+diabetes+insulin+thyroid hormone, levothyroxin sodium, 5.0 µg/kg for 5 weeks. After the genomic DNA of liver tissues was extracted, the ratio of 8-OHdG to deoxyguanosine and liver tissue protein oxidation markers was determined. The main findings of our recent study were the increased 8-OHdG levels during the diabetes, hypothyroidism, and hypothyroidism with diabetes, which can be regulated in different percentages with the treatment of 2.5 and 5.0 µg/kg doses of thyroid hormone and the altered protein carbonyl and AOPP levels of liver tissue. Consequently, it was observed that the DNA and protein damage induced by oxidative stress in diabetes could be regulated by dose-dependent thyroid hormone-mediated effects to insulin treatment.

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.

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.

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.

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 thyroid hormone mediated effects of insulin on serum leptin levels of diabetic rats.

In this study, we aimed to evaluate the possible relations of serum leptin and thyroid hormones on insulin treatment of surgically thyroidectomized and streptozotosin induced diabetic group of rats and whether the thyroid hormones control the leptin levels or leptin levels affect the thyroid hormones in DM. The Sprague-Dawley rats were assigned to eight groups: group 1, control; group 2, diabetes (injected intraperitoneally (i.p.) with streptozotocin (stz) 55 mg/kg); group 3, diabetes + insulin (rats were treated with insulin, 7-10 U/kg/day, subcutaneously); group 4, surgically thyroidectomized control; group 5, thyroidectomized + diabetes (3 weeks after the surgical operation, injected i.p. with stz); group 6, thyroidectomized + diabetes + insulin; group 7, thyroidectomized + diabetes + insulin + thyroid hormone (after diabetes induction, rats were treated with insulin and thyroid hormone, levothyroxin sodium (T4; 2.5 microg/kg); group 8, thyroidectomized + diabetes + insulin + thyroid hormone (T4; 5 microg/kg). The free and total T3 and T4 levels were measured in serum samples by otoanalyzer, and leptin levels were determined by ELISA method. The main finding of our recent study is that the decreased levels of serum leptin during the diabetes, hypothyroidism, and hypothyroidism with diabetes can be regulated in different percentages with the treatment of insulin and various doses of thyroid hormone. The observations in our study suggest the idea that during diabetic hypothyroidism, without thyroid hormone treatment, insulin is not sufficient to balance the metabolic pathways so mediated effects of insulin in leptin regulation via thyroid hormones are an increased possibility.

Advanced oxidation protein products, ferrous oxidation in xylenol orange, and malondialdehyde levels in thyroid cancer.

AIMS AND BACKGROUND: The oxidation of protein plays an essential role in the pathogenesis of an important number of degenerative and cancer diseases, which is now widely recognized. The aim is to examine advanced oxidation protein products (AOPPs), lipid peroxidation products malondialdehyde (MDA), and ferrous oxidation in xylenol orange (FOX) in blood samples of papillary thyroid cancer patients compared with healthy controls to determine the oxidation status and the change after thyroidectomy. METHODS: Thirty-five female thyroid cancer patients who underwent total thyroidectomy and 39 female control subjects were included into this study. Prethyroidectomy and postthyroidectomy, AOPP, FOX, and MDA levels were studied. RESULTS: Prethyroidectomy AOPP, FOX, and MDA levels were significantly higher compared to control (P < .05). In postthyroidectomy AOPP, FOX, and MDA levels were significantly decreased compared with prethyroidectomy levels (P < .05). However, postthyroidectomy levels on the 20th day were still significantly higher, compared to control subjects (P < .05). CONCLUSION: In conclusion, all of AOPP, FOX, and MDA levels that are markers of protein oxidation and lipid hyperoxidation may induce thyroid cancer development and begin to decrease after thyroidectomy.

Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations.

CONTEXT: Asymmetric dimethylarginine (ADMA) has recently emerged as an independent risk marker for cardiovascular disease, but studies investigating the ADMA levels in type 1 diabetes mellitus (DM) are scarce. OBJECTIVE: We aimed to evaluate plasma ADMA, L-arginine concentrations, and L-arginine to ADMA ratio in uncomplicated type 1 diabetic patients and controls. DESIGN AND SUBJECTS: Forty patients with type 1 DM who did not have clinical evidence of vascular complications and 35 healthy controls were included in the study. RESULTS: Plasma ADMA concentrations were higher (2.6 +/- 1.9 vs. 1.7 +/- 0.7 micromol/liter, P < 0.01), and L-arginine levels were lower (79.3 +/- 22.6 vs. 89.6 +/- 19.4 micromol/liter, P < 0.05) in the diabetic group, compared with controls. The L-arginine to ADMA ratio was also lower in the diabetic group (38.7 +/- 17.1 vs. 62.0 +/- 27.9, P < 0.0001). In diabetic patients, logADMA correlated positively with body mass index (BMI) (P = 0.01), fasting blood glucose (P = 0.006), and low-density lipoprotein cholesterol (LDL-c) (P = 0.01) and negatively with high-density lipoprotein cholesterol (P = 0.03). L-arginine to ADMA ratio correlated negatively with BMI (P = 0.004), fasting blood glucose (P = 0.02), and LDL-c (P = 0.01) and positively with high-density lipoprotein cholesterol (P = 0.04). In controls, logADMA and L-arginine to ADMA ratio correlated with BMI and LDL-c (P < 0.05). In regression analysis, BMI predicted 15% variance of ADMA levels (P = 0.02). CONCLUSIONS: We demonstrated that ADMA increases and L-arginine to ADMA ratio decreases, even before the development of vascular complications in type 1 DM.

Erythrocyte glutathione levels in lithium-induced hypothyroidism.

BACKGROUND 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 600-1200 mg 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.

Effect of the sulphonylurea glibenclamide on liver and kidney antioxidant enzymes in streptozocin-induced diabetic rats.

BACKGROUND: 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.

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.

Lipid peroxidation and scavenging enzyme levels in the liver of streptozotocin-induced diabetic rats.

In this study, alterations in the liver antioxidant enzymes status and lipid peroxidation in short-term (8-weeks) and long-term (24-weeks) diabetic rats were examined. Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) levels were significantly increased, but superoxide dismutase (SOD) activity was significantly reduced in 8-weeks diabetic rats, compared to control. Catalase (CAT) activity, however, was found unchanged. In 24-weeks diabetic rats, while GSH-Px activity was unchanged, but SOD and CAT activities and MDA levels were significantly increased, compared to control. These results suggest that diabetes-induced alterations in tissue antioxidant system may reflect a generalized increase in tissue oxidative stress. It can be concluded that lipid peroxidation and antioxidant enzyme levels are elevated in diabetic condition. Hence, diabetes mellitus, if left untreated, may increase degenerative processes due to accumulation of oxidative free radicals.