Hüsrev Hatemi

Antioxidant status in experimental hyperthyrodism: effect of vitamin E supplementation

Free radical-mediated oxidative stress has been implicated in the genesis and exacerbation of degenerative diseases. In view of the role of oxidative processes in hyperthyroidism, in this study, we investigated the antioxidant status of erythrocytes in experimental hyperthyroidism and the effect of vitamin E supplementation on defense systems. Our findings of significantly increased T4 and T3 and undetectable TSH values in thyroxine administered rats confirmed the establishment of hyperthyroidism. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (GSH) values were found to be significantly increased in hyperthyroid rats in comparison to the control group. Vitamin E supplementation to hyperthyroid rats induced a significant decrease in GSH-Px activity and a significant increase in GSH level. These findings show that hyperthyroidism increases the components of the antioxidant system in the erythrocytes. Furthermore, vitamin E supplementation reduces the burden of oxidative stress in hyperthyroidism.

Erythrocyte osmotic fragility and oxidative stress in experimental hypothyroidism.

The present study was planned to explain the relation between erythrocyte osmotic fragility and oxidative stress and antioxidant statue in primary hypothyroid-induced experimental rats. Twenty-four Spraque Dawley type female rats were divided into two, as control (n=12) and experimental (n=12), groups weighing between 160 and 200 g. The experimental group animals have received tap water methimazole added standard fodder to block the iodine pumps for 30 d (75 mg/100 g). Control group animals were fed tap water and only standard fodder for the same period. At the end of 30 d blood samples were drawn from the abdominal aorta of the rats under ether anesthesia. T3, T4, and TSH levels were measured and the animals that had relatively lower T3, T4, and higher TSH levels were accepted as hypothyroid group. Hormone levels of the control group were at euthyroid conditions. Osmotic fragility, as a lipid peroxidation indicator malondialdehyde (MDA), antioxidant defense system indicators superoxide dismutase (SOD) and glutathione (GSH) levels were measured in the blood samples. Osmotic fragility test results: There was no statistically significant difference found between maximum osmotic hemolysis limit values of both group. Minimum osmotic hemolysis limit value of hypothyroid group was found to be higher than that of control group values (p<0.02). The standard hemolysis and hemolytic increment curve of the hypothyroid group drawn according to osmotic fragility test results was found to be shifted to the right when compared to control group’s curve. This situation and hemolytic increment value, which shows maximum hemolysis ratio, is the proof of increased osmotic fragility of the erythrocytes in hypothyroidism. There is no statistically significant difference found between hypothyroid and control groups in the lipid peroxidation indicator MDA and antioxidant indicators SOD and GSH levels. As a result of our study it may be concluded that hypothyroidism may lead to an increase in osmotic fragility of erythrocytes. But the increase in erythrocyte osmotic fragility does not originate from lipid peroxidation.

The erythrocyte glutathione levels during oral glucose tolerance test

Erythrocytes glutathione (GSH) levels were measured in erythrocytes from 33 subjects, at baseline and after 2-hour glucose loading in order to investigate the effect of glucose ingestion on the erythrocyte GSH. According to the World Health Organisation criteria 18 subjects had normal glucose tolerance (NGT) (mean age 48±10 years, 10 women, 8 men), 15 subjects had impaired glucose tolerance (IGT) (mean age 52±8 years, 9 women, 6 men). After 12-hour fasting, erythrocyte GSH levels were 40.5±8.06 and 39.27±10.26 mg/dl hemolisate in subjects with NGT and IGT, respectively (p=N.S). After 2-hour glucose loading, erythrocyte GSH levels decreased to 36.01 ±9.4 (p<0.05) and 32.36±5.7 (p<0.005) in subjects with NGT and IGT, respectively. The decrease in erythrocyte GSH levels in subjects with IGT was greater than in NGT individuals (p<0.001). There was negative correlation between glucose, insulin, C-peptide, and erythrocyte GSH levels after glucose loading (p<0.005). Our results suggest that glucose loading induce an oxidative stress in all subjects but this oxidative stress is greater in subjects with IGT than with NGT.

CALCIUM, MAGNESIUM, AND ZINC STATUS IN EXPERIMENTAL HYPERTHYROIDISM

In this study, experimental hyperthyroidism was established and used to investigate possible alterations in the calcium (Ca), magnesium (Mg), and zinc (Zn) homeostasis by assessing their concentrations in plasma and erythrocytes.In the L-thyroxine-induced hyperthyroidism condition, the experimental animals show a significant decrease in erythrocyte Ca, Mg, and Zn concentrations, and a significant decrease in plasma Mg concentration. Significant positive correlations were found for Mg and Zn both in plasma and in erythrocytes.The results suggest that the homeostasis of Ca, Mg, and Zn is altered during experimental hyperthyroidism.

Biochemical Evaluation of Oxidative Stress in Propylthiouracil Treated Hyperthyroid Patients. Effects of Vitamin C Supplementation

Abstract In this study the impact of vitamin C supplementation on oxidative damage as assessed by thiobarbituric acid reactive substances and markers of antioxidant status: namely Cu/Zn superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione were investigated in 24 hyperthyroid patients under propylthiouracil therapy (3×100 mg/day) for five days and in 15 healthy controls. Ascorbic acid (1000 mg/day) was given as a supplement for 1 month to both the patients and controls during the study period. Heparinised blood samples were taken at the beginning and the end of one month ascorbic acid supplementation. Comparison of the hyperthyroid patients with the controls revealed higher lipid peroxidation (p<0.001), higher Cu/Zn superoxide dismutase activity (p<0.001), higher glutathione level (p<0.001) and lower glutathione reductase activity (p<0.001). Vitamin C supplementation to hyperthyroid patients caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase activity (p<0.001), whereas there were significant decreases in glutathione reductase (p<0.001) and Cu/Zn superoxide dismutase activities (p<0.01). Thiobarbituric acid reactive substances and thiobarbituric acid reactive substances/glutathione ratio were significantly decreased (p<0.01). Vitamin C supplementation to euthyroid controls caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase and Cu/Zn superoxide dismutase activities (p<0.001), whereas there was a significant decrease in glutathione reductase (p<0.001). The thiobarbituric acid reactive substances/glutathione ratio was significantly decreased (p<0.05). Our findings reveal the potentiation of antioxidant status and a relief in oxidative stress in both propylthiouracil treated hyperthyroid patients and controls in response to vitamin C supplementation.

Oxidative stress in heart tissue of hyperthyroid and iron supplemented rats.

This study was designed to investigate the effect of hyperthyroidism and/or iron supplementation on cardiac oxidative stress parameters--the lipid peroxidation end product glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (CuZnSOD)--in rats. In plasma, ferritin as an indicator of iron status and glutamate oxaloacetate transaminase (GOT) as an indicator of damage to the heart tissue were analyzed. Our findings show that hyperthyroidism increased lipooxidative damage as reflected by higher lipid peroxidation end product levels and elevated antioxidant defense parameters--GSH and GSH-Px. Iron supplementation per se does not affect oxidative stress parameters studied in the euthyroid state. Although iron increased lipid peroxidation in the hyperthyroid state, this effect was less than that seen in euthyroidism. Iron supplementation to hyperthyroid rats significantly lowered plasma ferritin levels, suggesting increased iron elimination with consequently reduced oxidative stress.

Prevalence of Overweight and Obesity in Turkey

The objectives of this study were to determine the prevalence of overweight and obesity in Turkey, and to investigate their association with age, gender, and blood pressure. A crosssectional population-based study was performed. A total of 20,119 inhabitants (4975 women and 15,144 men, age > 20 years) from 11 Anatolian cities in four geographic regions were screened for body weight, height, and systolic and diastolic blood pressure between the years 1999 and 2000. The overall prevalence rate of overweight was 25.0% and of obesity was 19.4%. The prevalence of overweight among women was 24.3% and obesity 24.6%; 25.9% of men were overweight, and 14.4% were obese. Mean body mass index (BMI) of the studied population was 27.59 +/- 4.61 kg/m(2). Mean systolic and diastolic blood pressure for women were 131.0 +/- 41.0 and 80.2 +/- 16.3 mm Hg, and for men 135.0 +/- 27.3 and 83.2 +/- 16.0 mm Hg. There was a positive linear correlation between BMI and blood pressure, and between age and blood pressure in men and women. Obesity and overweight are highly prevalant in Turkey, and they constitute independent risk factors for hypertension.

EFFECT OF SEX HORMONES ON LIPID PEROXIDATION IN WOMEN WITH POLYCYSTIC OVARY SYNDROME, HEALTHY WOMEN, AND MEN

Recently, the influence of free radicals and lipid peroxides on many diseases, the effect of sex hormones on lipid peroxidation and antioxidant effects of estrogens have received considerable interest. In the present study we aimed to investigate the relationship between sex hormones and both lipid peroxidation and glutathione content in women with polycystic ovary syndrome (POS), in healthy women and in healthy men. We measured levels of lipid peroxides and sex hormones in plasma and levels of glutathione in erythrocytes of all cases. We evaluated the level of thiobarbituric acid reactive substances (TBARS) as an index of lipid peroxides and erythrocyte glutathione level as an index of antioxidant. We found that plasma levels of free testosterone, dehydroepiandrosterone sulfate (DHEAS) and estradiol significantly higher in the women with POS group than in the healthy women group. There was no significant difference in the levels of both plasma TBARS and erythrocyte glutathione, between women with POS group and healthy women group. Plasma DHEAS levels of healthy men and women with POS were similar. Plasma TBARS level was higher and erythrocyte glutathione level was lower in the healthy men group than in both the healthy women group and in the women with POS group. These data imply that testosterone has an oxidant effect. DHEAS which is an antioxidant, has a protective role in females with POS. Estrogens have an antioxidant effect but this action changes according to its dominant degradation pathway.

The susceptibility of red blood cells to autoxidation in type 2 diabetic patients with angiopathy.

We examined the in vitro susceptibility of red blood cell (RBC) lipids to oxidation in type 2 diabetic patients with or without angiopathy. Lipid peroxidation was assessed by quantifying thiobarbituric acid (TBA) reactivity as malondialdehyde (MDA). We also examined the RBC antioxidant status by determining glutathione (GSH) levels. Before in vitro oxidation, RBC MDA levels were significantly higher in both diabetic groups than in the controls (P < .001), and a significant difference was found between the two diabetic groups (P < .05). After in vitro treatment of RBCs with hydrogen peroxide, the degree of lipid peroxidative damage was significantly higher in diabetic patients with angiopathy versus diabetics without angiopathy (P < .001). Diabetic patients have low RBC GSH levels compared with controls, and after in vitro oxidation, the levels were significantly decreased in diabetics (P < .001). There was not a significant correlation between RBC MDA levels and glycated hemoglobin (GHb), plasma cholesterol, and triglyceride. The correlation between RBC MDA and GSH was weak (P < .001). We suggest that the results of this study might help to clarify the role of oxidative mechanisms as an in vitro model of degenerative damage in type 2 diabetic angiopathic complications.

EARLY CHANGES IN PARAMETERS OF BONE AND MINERAL METABOLISM DURING THERAPY FOR HYPER- AND HYPOTHYROIDISM

The effects of thyroid hormones on various organs and metabolic systems have been the focus of intensive research. In this study we investigated the mechanisms of the changes in some parameters of bone and mineral metabolism before and during treatment of hyper- and hypothyroidism. Our study groups were as follows; 1) Untreated hyperthyroid patients (n = 38), 2) Hyperthyroid patients treated for three months (n = 21), 3) Untreated hypothyroid patients (n = 27), 4) Hypothyroid patients treated for three months (n = 20), and 5) Euthyroid control subjects (age, weight, sex and menopausal status matched) (n = 47). As expected, the mean serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and urinary Ca/creatinine and deoxypyridinoline (D-Pyr)/creatinine levels were higher in group-1 than in the control group. Serum PTH level was lower in group-1 than in group-5. However, after treatment for three months (group-2) we found that the serum and urinary levels of these parameters (except ALP) were not different than in the control group. Group-3 and group-4 did not show any differences in these parameters compared with group-5. Covariance analysis showed that urinary D-Pyr excretion had a positive, independent relationship to the serum free T3 level and age (P < 0.001 and P = 0.02, respectively). These results suggest that both bone formation and resorption markers increase in hyperthyroid patients, and with the treatment, particularly, in the period of first three months the bone resorption markers decrease rapidly. If the treatment is maintained the decrease slows, becoming more gradual. However, bone formation markers like ALP remain high in hyperthyroid patients during the treatment. In the light of this data, it is possible to conclude that osteoblastic activity lasts longer in hyperthyroidism. On the other hand, we demonstrated that these bone formation and resorption markers do not seem to be different in hypothyroid patients, even during the treatment, compared to the euthyroid controls.