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PREDISPOSITION TO ENDOTHELIAL DYSFUNCTION IN EXPERIMENTAL SUBCLINICAL HYPOTHYROS

Subclinical hypothyroidism (SH) or mild thyroid failure reflect declined thyroid activity without clear symptoms, but with elevated thyroid stimulating hormone (TSH) and normal range free thyroxine (FT4) and triiodothyronine (FT3) as the diagnostic indicators. Thyroid hormones are associated with the oxidative and antioxidative status of the organism. Depression of metabolism due to hypothyroidism has been showed to decrease oxidant production and thus protects tissues against oxidant damage. Lipid peroxidation is reported to be high in hyperlipidaemia, which is a consistent biochemical feature in hypothyroidism. However, data on the oxidative status of hypothyroidism are limited and controversial.The endothelial dysfunction, is one of the earliest signs for atherosclerosis, which frequently observed in experimental and clinical investigations, prior to any overt manifestations of SH. The predisposition to ED under condition of atherosclerosis may be partially explained by the factors including changes in lipid profile, oxidative stress, disturbances in NO synthesis. Therefore, endothelial dysfunction would be a favorable triger factor to investigate the correlation between SH and cardiovascular disease. Taking it into consideration, the present study was trying to establish novel aspects linking SH and endothelial function. ?he experiments were carried out on the intact male rats (weight 180-220 g, control and experimental group). The model of mild thyroid failure was induced by the oral administration of mercazolilum in doses of 3 mg/kg during 3 weeks. (method, proposed by E.S.Detyuk et al.). Function of thyroid gland was assessed by the serum concentrations of thyroid hormones - thyroxine (FT4) and triiodothyronine (FT3), thyroid stimulating hormone (TSH) by radioimmunoassay analysis. Total cholesterol (TCh), high-density lipoprotein cholesterol (HDL), low-density lipoprotein (LDL), atherogenic index, the biomarkers of lipid peroxidation system - diene conjugates (DC) and thiobarbituric acid reactive substances (TBARSs), activity of antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) as well as metabolites of nitric oxide - nitrit-ion, under conditions of hypothyrosis were determined. Parameters of free radical peroxide reactions were investigated in comparative interaction with enzymatic antioxidant defense. Activation of lipoperoxidation (LPO) processes has been established in rat blood. The concentration of thiobarbituric acid reactive substances in the blood significantly exceeds parameters of control values (due to the content of MDA – 27 %, DC – 46 %.). Enzymatic protection against reactive oxygen species (ROS) and the breakdown products of peroxidized lipids are provided by superoxide dismutase (SOD) and catalase (CAT). Correspondively, the activity of antioxidant protection system was depressed (SOD – by 30.5%, GPx - by 37.1% compared to normal values). These data suggest the impairment of the antiradical protective link. A relationship between mild hypothyrosis and dislipidemia was established. Increase in serum levels of low-density lipoprotein, and reduction in HDL, and as a result, increase in atherogenic index (0,530 ± 0,035) has been shown. With respect to parameters of nitric oxide system, the decreased level of nitrite-ion in rat blood, has been also demonstrated. It should be emphasized that the observed changes can predict the tendency to endothelial dysfunction in SCH. In conclusion, our study showed the changes in blood of the lipid profile, decrease in nitrit-ion concentration, activation of lipid peroxidation processes. It can be qualified as metabolical and functional precondition of endothelium disfunction under mild defficiency of thyroid hormones. However, further studies are necessary to evaluate a larger series of experimental groups, with a wider spectrum of biomarkers to analyze correlation between different links of metabolism in condition of mild hypothyroid function.



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Keywords: subclinical hypothyroidism, endothelial dysfunction, lipid profile, oxidative stress, nitri? ion

ISSN: 1609-6371

EISSN: 1609-6371

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