Erythrocyte osmotic fragility and lipid peroxidation in experimental hyperthyroidism.

This study investigated the relation between erythrocyte osmotic fragility and oxidative stress and antioxidant state in primary hyperthyroidism induced experimental rats. Twenty-four Spraque-Dawley-type female rats weighing between 160 and 200 g were divided into two, as control (n = 10) and experimental (n = 12), groups. The experimental group animals have received tap water and L-Tiroksin (0.4 mg/100 g fodder) added standard fodder for 30 days to induce hyperthyroidism. Control group animals were fed tap water and standard fodder for the same period. Blood samples were drawn from the abdominal aorta of the rats under ether anesthesia. T3, T4, and TSH levels, osmotic fragility, malondialdehyde (MDA), superoxide dismutase, and glutathione levels were measured in the blood. There was a statistically significant deviation found in maximum and minimum osmotic hemolysis limit values of experimental group when compared to controls. The standard hemolytic increment curve of the hyperthyroid group shifted to the right when compared to control group's curve. There was a statistically significant increase found in MDA and superoxide dismutase, but statistically a significant decrease was detected in glutathione levels in hyperthyroid group when compared to controls. As a result of our study, it may be concluded that hyperthyroidism may led to an increase in osmotic fragility of erythrocytes and this situation may possibly originate from the increased lipid peroxidation in hyperthyroidism.

Investigation of tissue factor and other hemostatic profiles in experimental hypothyroidism.

The influence of thyroid failure on hemostasis has been studied and is still not well understood. These patients have high risk for cardiovascular diseases because of the lipid metabolism and procoagulant agents. But the influence of thyroid failure on hemostasis is controversial. Tissue factor (TF) has an important role in the thromboembolic state. Recent experiments have demonstrated that TF-dependent activation of the coagulation cascade plays an important role in the pathophysiology of intravascular thrombus formation. The purpose of the present study was to investigate the contributions of TF, factor VII:C (FVII:C), factor XII:C (FXII:C), and fibrinogen in experimental hypothyroidism. TF was obtained from the thyroid gland and lung tissue of 10 rats following experimental hypothyroidism induced for 30 d and compared with similar tissue from 10 control rats. Significantly increased TF activities were found in hypothyroid rats. By contrast, FVII:C level was significantly decreased when compared with the control group. In this respect it is interesting to note that a hypercoagulable state due to increased thromboplastic activity may occur. Based on those results, elevated tissue factor activities (TFa) of the patients with low thyroid dysfunction may have another risk factor for cardiovascular diseases.

Bone metabolism in ovariectomized rats with induced hyperthyroidism: the effect of estrogen replacement.

We aimed to investigate whether or not the estrogen is playing any role in the effect of thyroid hormones on bone metabolism. The rats were divided into five groups. In the first group L-thyroxine-induced hyperthyroid rats were ovariectomized (OVX) while the OVX rats were administered L-thyroxine in the second group. 17beta-Estradiol (E2) was replaced in OVX rats in Group III. L-thyroxine and E2 were simultaneously administered to OVX rats in Group IV. The fifth group received sham operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)alpha, calcium (Ca), phosphorous (P), parathyroid [corrected] hormone (PTH), alkaline phosphatase (t-ALP), bone-specific alkaline phosphatase (b-ALP) and E2. The levels of cytokines, t-ALP and b-ALP increased but PTH decreased, while there was no change in Ca and P levels in L-thyroxine-administrated rats. However, the levels of cytokines, Ca, P, PTH, t-ALP and b-ALP did not change in L-thyroxine-administered OVX rats. In OVX rats, the cytokines, t-ALP and b-ALP increased while Ca, P remained the same, but PTH decreased. L-thyroxine administration to OVX rats did not change the cytokines, Ca, P, PTH, t-ALP and b-ALP levels. The replacement of E2 in OVX rats decreased the cytokines, t-ALP and b-ALP values, increased PTH levels while there was no change in Ca and P. L-thyroxine and E2 administration to OVX rats increased the cytokines, t-ALP and b-ALP levels and decreased PTH, but Ca and P remained the same. In sham-operated rats, there was no change in all parameters compared to initial values. This study suggests that estrogen may play a role in the effects of thyroid hormones on bone metabolism.

The role of nitric oxide on bone metabolism in ovariectomized rats following chronic ethanol intake.

This experimental study was designed to examine the effect of nitric oxide (NO) on bone metabolism in ovariectomized rats following chronic ethanol treatment. Chronic ethanol intake was produced by gradual substitution (within 3 weeks) of tap water in diet with 5,10,15 and finally 20% of ethanol. Thereafter, the rats were maintained under these conditions for a duration of 4 months. The rats were divided into two groups. The first group received sham operation (SHAM) and the rats in Group II were ovariectomized (OVX). Five weeks after the SHAM and ovariectomy, the rats were treated with ethanol for 4 months. After this period of ethanol administration, the NOS inhibitor N(W)-nitro-L-arginine methyl ester (L-NAME) was given for three weeks along with ethanol to the same rats. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, NO, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), 25 HydroxyvitaminD3 [25(OH)D3], alkaline phosphatase (ALP), bone alkaline phosphatase (b-ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), gamma-glutamyltransferase (GGT) levels were measured in different stages of the experiment. IL-1beta, IL-6, TNFalpha and NO levels increased after ethanol administration in SHAM and OVX rats. The decrease in serum Ca was significant while the changes in P, PTH and 25 (OH)D3 levels were not. ALP and b-ALP levels were significantly decreased; ALT, AST and GGT levels were significantly increased. In ovariectomized and SHAM rats, administration of L-NAME together with ethanol, produced a significant increase in IL-1beta, IL-6 and TNFalpha levels. In this group, Ca and P levels were significantly increased, PTH and 25 (OH)D3 levels were significantly decreased. Also, there was a significant decrease in ALT, AST, ALP, b-ALP, and GGT levels. NO increase due to alcohol intake may function as a protective mechanism preventing bone resorption in cases of estrogen insufficiency.

The effects of experimental hypothyroidism on hemorheology and plasma fibrinogen concentration.

Effects of hypothyroid on hemorheology of patients had widely attracted the attention of researchers during last decade. The present study has been planned with the purpose to determine the effects of experimental hypothyroidism on hemorheological parameters and fibrinogen concentration. To induce experimental hypothyroid methimazole (75 mg/100 g) was added to the fodder of an experimental group rats for 20 d. After experimental duration, plasma and blood viscosity, hematocrit (Hct), hemoglobin, erythrocyte rigidity index, and plasma fibrinogen concentration values of both the control and the experimental group animals were determined and evaluated. The serum T3 and T4 levels of the experimental group were found lower (p < 0.001) but TSH level higher (p < 0.001) than that of the control group. Plasma viscosity and fibrinogen concentration of hypothyroid group were found significantly higher than controls (p < 0.01). Hematocrit and hemoglobin values were also found lower in the experimental group than the control group animals (p < 0.01). However, there was no significant difference found in blood viscosity at the original Hct value but there was a significant increase at standard Hct value (p < 0.01). There was also no change in erythrocyte rigidity index between control and experimental groups. According to these results it may be said that in hypothyroidism, increased fibrinogen concentration may alter the rheological structure of blood by inducing increase in plasma viscosity.

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.

Iron supplementation in experimental hyperthyroidism: effects on oxidative stress in skeletal muscle tissue.

This study was designed to investigate the effects of iron supplementation on the parameters of oxidative stress in the skeletal muscle tissue of hyperthyroidism induced rats. Hyperthyroidism was found to cause an increase in thiobarbituric acid-reactive substances (TBARS) and copper zinc superoxide dismutase (Cu, Zn SOD) activity, but decreases in the glutathione-peroxidase (GSH Px) activity and glutathione (GSH). Iron supplementation caused an increase in TBARS and a decrease in GSH. Iron supplementation in hyperthyroid rats attenuated the hyperthyroid state, but lowered the plasma ferritin level, which is considered an indicator of thyroid hormone action. Iron supplementation caused no additional increase in the TBARS in hyperthyroid rats, ameliorated the decrease in GSH content and abolished the induction of Cu, Zn SOD. Our findings suggested no increase, but a decrease, in the risk of oxidative stress in iron supplemented hyperthyroid rats. Whether supplementation of iron would have similar effects in humans should be further investigated in clinical studies.

Oxidative damage to nuclear DNA in hyperthyroid rat liver: inability of vitamin C to prevent the damage.

The effects of hyperthyroidism on oxidative DNA damage in liver tissue and modification by vitamin C supplementation were investigated in rats. Animals were rendered hyperthyroid by administration of L-thyroxine (0.4 mg/100 g food) for 25 d. In the plasma samples, T(3), T(4), and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay and ascorbate spectrophotometrically. Oxidative damage to hepatic nuclear DNA was determined by measuring deoxy-guanosine (dG) and 8-oxodG by high-performance liquid chromatography with diode array detector electrochemical detection (HPLC-DAD-ECD). In hyperthyroidism, 8-oxodG/(10(5) dG) levels were significantly higher and plasma vitamin C levels lower than in control rats. The results of this experimental study show that oxidative damage to hepatic nuclear DNA increases in the hyperthyroid state and that vitamin C was not effective in preventing this damage.

Effects of osteoporotic cytokines in ovary-intact and ovariectomised rats with induced hyperthyroidism; is skeletal responsiveness to thyroid hormone altered in estrogen deficiency?

This experimental study was designed to examine the effects of hyperthyroidism on osteoporotic cytokines such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in the physiological concentrations and in the deficiency of estrogen. We investigated the effects of thyroid hormones on cytokines and bone metabolism in L-thyroxine induced ovary-intact and ovariectomised rats, as levels of cytokines were increased in hyperthyroidism. The rats were divided into three groups. In the first group, L-thyroxine-induced hyperthyroid rats were ovariectomised (OVX), while the OVX rats were administered L-thyroxine in the second group. The third group received sham-operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (b-ALP). L-thyroxine administration increased the cytokines, ALP and b-ALP and decreased PTH, while there was no change in Ca and P. However, the ovariectomy of these rats did not change the levels of cytokines, Ca, P, PTH, ALP, and b-ALP. In ovariectomised rats, the cytokines, ALP and b-ALP increased but not Ca and P conversely, PTH decreased. L-thyroxine administration to ovariectomised rats did not change the levels of cytokines, Ca, P, PTH, ALP and b-ALP. In sham-operated rats there was no change in any of the parameters compared with initial values. Thyroid hormones may not be effective on bone metabolism in estrogen deficiency.

Nitric oxide synthase inhibition by L-NAME in streptozotocin induced diabetic rats: impacts on oxidative stress.

The effects of nitric oxide synthase (NOS) inhibition by Nw-nitro-L-arginine methyl ester (L-NAME) administration on oxidative stress parameters were investigated in streptozotocin (STZ) induced diabetic rats. Lipid peroxidation as reflected by thiobarbituric acid reactive substances (TBARS) was insignificantly higher in diabetic rats. Plasma NO2+NO3 values (p < 0.05) and erythrocyte CuZn superoxide dismutase (CuZn SOD) and glutathione peroxidase (GSH Px) activities were significantly higher (p < 0.01, p < 0.001, respectively) in diabetic rats. L-NAME administration to diabetic rats caused significantly lower CuZn SOD and GSH Px activities (p < 0.01) and NO2+NO3 values (p < 0.001), whereas a significantly higher GSH level (p < 0.01). TBARS/GSH ratio was significantly higher in diabetic rats than controls (p < 0.05) and significantly lower in L-NAME administered diabetic rats than diabetic rats (p < 0.05). This experimental study highlightens the importance of NOS inhibition by L-NAME in the attenuation of oxidative stress in STZ diabetic rats.