propylthiouracil and Arteriosclerosis

Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.. Twenty patients with hyperthyroidism, 20 patients with euthyroid multinodular goiter (MNG) and 20 age- and sex-matched healthy controls were enrolled in the study. Insulin sensitivity index, PON activity and lipid peroxidation were measured at baseline and 2 months after achieving euthyroidism or subclinical hyperthyroidism. Levothyroxine was given as a part of TSH suppression therapy in multinodular goitre patients.. Insulin sensitivity was determined by an oral glucose tolerance test (OGTT) based on the insulin sensitivity index (ISI) formula, serum paraoxonase activity was determined with a spectrophotometric method. Lipid peroxidation was measured by the formation of thiobarbituric acid reactive substances (TBARs).. ISI was significantly lower in the hyperthyroid group than baseline levels in MNG patients and controls (P < 0.001). While ISI increased after treatment in the hyperthyroid group (P < 0.01), it significantly decreased with L-T4 treatment in the MNG group (P < 0.01). Serum paraoxonase activity was significantly lower in the hyperthyroid group before treatment than baseline and final measurements of other groups (P < 0.05). While PON activity increased after restoration of the euthyroid state in the hyperthyroid group (P < 0.05), it decreased with L-T4 treatment in the MNG group (P < 0.05). Lipid peroxidation was significantly higher in hyperthyroid group compared to baseline levels of other groups (P < 0.05). It decreased after treatment in the hyperthyroid group (P < 0.05) but a significant increase was observed following L-T4 treatment in the MNG group (P < 0.05). Serum paraoxonase activity was found to be negatively correlated with serum TT4 (r = -0.32, P = 0.003), TT3 levels (r = -0.31, P = 0.004), TBARs levels (r = 0.32, P = 0.003) and positively correlated with ISI (r = 0.35, P = 0.001) and high-density lipoprotein (HDL) cholesterol levels (r = 0.35, P = 0.0011) in the hyperthyroid and MNG groups.. Iatrogenic thyroid hormone excess seems to mimic the effects of endogenous thyroid hormone excess on paraoxonase activity, insulin sensitivity and oxidative stress. These findings suggest that TSH suppression with levothyroxine may increase oxidative stress and LDL oxidation and thereby promote atherogenesis.

Topics: Adult; Analysis of Variance; Antithyroid Agents; Arteriosclerosis; Aryldialkylphosphatase; Case-Control Studies; Female; Goiter, Nodular; Humans; Hyperthyroidism; Insulin Resistance; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Propylthiouracil; Thyroid Function Tests

Many of the morphologic and biochemical features of porcine coronary atherosclerosis produced by high cholesterol, high fat diet and propoylthiouracil returned to control values after cessation of the atherogenic regimen. These include disappearance of foam cells and a decrease in lipid content, DNA concentration, and DNA and protein synthesis. The morpholigic and biochemical features of te atherosclerotic lesions described herein were similar to those produced in swine and other species by a variety of inciting agents during both the progression and regression phase of the disease. These results indicate that the porcine propylthiouracil-diet model may be useful for the study of coronary lesions. Second, the similarities of response of arterial tissue in several experimental animals suggest the possibility that human coronary lesions by analogy may regress under therapeutic regimens.

Topics: Animals; Arteriosclerosis; Cholesterol; Cholesterol, Dietary; Dietary Fats; Lipid Metabolism; Propylthiouracil; Swine

Topics: Arteriosclerosis; Atherosclerosis; Bile Acids and Salts; Butter; Cholesterol; Diet; Diet, Atherogenic; Infarction; Myocardial Infarction; Oils; Pathology; Propylthiouracil; Rats; Research; Salts; Thrombosis; Toxicology; Zea mays

Topics: Aortic Diseases; Arteriosclerosis; Atherosclerosis; Barium Sulfate; Blood Coagulation; Dietary Fats; Hyperlipidemias; Lipid Metabolism; Portal Vein; Propylthiouracil; Rats; Research; Thrombosis

Topics: Adrenal Glands; Animals; Arteriosclerosis; Atherosclerosis; Blood Proteins; Body Weight; Cholesterol; Heart; Hypothyroidism; Iodine Isotopes; Lipids; Liver; Pharmacology; Physiology; Pituitary Gland; Propylthiouracil; Rabbits; Research; Thyroid Gland; Thyroidectomy; Thyroxine