thiouracil and Hypercholesterolemia

The aim of this study was to investigate the antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 (estra-1,3,5(10),8-tetraene-3, 17 alpha-diol), having a non-feminizing effect and high antioxidant potential, in male rabbits.. Male White-Russian rabbits weighing 2.1-2.6 kg were fed either a standard or a high-cholesterol (200 mg/kg) diet, with thyroid function-inhibiting thiouracil (20 mg/kg) combined with cholic acid (40 mg/kg) administered daily in sunflower oil for 3 months. During the last month of the study, estrogens were administered by gavage at a dose of 0.02 or 0.1 mg/kg.. All three estrogens exerted remarkable antiatherosclerotic effects. Decreases in serum and aortic-wall lipid parameters and the index of atherogenicity were dependent on estrogen dose. Morphological evaluation of the aortic wall (height of plaques, size of plaque relative to aortic half-circumference) showed only weak therapeutic effects with all three estrogens. It is an open question whether the treatment period was too short to reverse the above changes. On the other hand, the data clearly suggest that 17 alpha-estradiol and J811 offer new perspectives for the prevention of atherosclerosis in men, which is similar to that found with 17 beta-estradiol in women.

Topics: Animals; Anticholesteremic Agents; Antithyroid Agents; Arteriosclerosis; Cholesterol, HDL; Diet, Atherogenic; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Estradiol; Free Radical Scavengers; Hypercholesterolemia; Male; Rabbits; Random Allocation; Sex Characteristics; Thiouracil

The effect of melatonin on cholesterol metabolism in the rat was investigated in the dietary and hypothyroid models of hypercholesterolemia. In normal and dietary hypercholesterolemia (induced by 1% cholesterol, 0.5% bile acid), melatonin treatment (12.5mg/kg i.p.) reduced total serum cholesterol concentration and total low density lipoprotein (VLDL+LDL) cholesterol. The protective action of melatonin was manifested only following the induction of cholesterolemia in such animals. Enhanced catabolism of cholesterol to bile acids is likely involved as shown by an increase in fecal bile acid excretion following melatonin treatment. Incorporation of 1-14C acetate into sterols was unaffected by melatonin treatment which suggests its lack of influence on sterol biosynthesis. In secondary hypercholesterolemia (hypothyroidism induced by 2-thiouracil), melatonin exerted a beneficial effect by increasing the HDL/total LDL cholesterol ratio. These findings suggest that the hypocholesterolemic effect of melatonin may work through the augmentation of endogenous cholesterol clearance mechanisms. This is accompanied by the lowering of the cholesterol fraction associated with low density lipoproteins.

Topics: Animals; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Feces; Homeostasis; Hypercholesterolemia; Hypothyroidism; Male; Melatonin; Rats; Rats, Sprague-Dawley; Thiouracil

We studied the effects of clentiazem, a calcium channel blocker (1) on the accumulation of lipid in the aorta, (2) on the level of plasma lipids, and (3) on the number of adherent intimal monocytes and foam cells. Seventy Wistar rats were assigned to one of the following groups: (1) regular diet, (2) an atherogenic diet consisting of regular chow with 2% cholesterol, 1% cholic acid, and 0.5% thiouracil (CCT), (3) CCT supplemented with 5 mg/kg/day clentiazem, and (4) CCT with 25 mg/kg/day clentiazem. Animals were sacrificed after 6 or 12 weeks of diet. Aortas were studied by light microscopy after staining with oil red O (ORO) and/or hematoxylin. ORO staining was quantified in both abdominal and thoracic regions of the aorta. The aortas of the clentiazem groups demonstrated significantly less ORO staining than CCT diet controls in thoracic aorta after 6 weeks and abdominal aorta after 12 weeks. There was no significant difference in the plasma lipid concentrations. The clentiazem-treated groups had fewer numbers of adherent monocytes and foam cells. We conclude that clentiazem inhibits lipid deposition in cholesterol-fed rats without lowering plasma lipid concentrations and that the number of intimal monocytes and foam cells is decreased in the presence of this calcium antagonist.

Topics: Animals; Aorta; Blood Pressure; Body Weight; Calcium Channel Blockers; Cell Adhesion; Cell Count; Cholesterol; Cholic Acids; Diet, Atherogenic; Diltiazem; Heart Rate; Hypercholesterolemia; Lipid Metabolism; Lipids; Male; Models, Biological; Monocytes; Rats; Rats, Wistar; Thiouracil

Effects of additions of amino acids to a 20% casein diet on serum cholesterol (Ch) were studied in hypothyroid and hepatoma-bearing rats with endogenous hypercholesterolemia as well as in normal rats. In normal Wistar rats, methionine (Met) was hypercholesterolemic at the "nutritional" level (0.2-0.4%), but hypocholesterolemic at the "excess" level (1.2-2.4%). In Wistar rats with hypothyroidism induced by thiouracil, the addition of excess (1.2%) Met to the 20% casein diet reduced an endogenous hypercholesterolemia due to hypothyroidism by suppressing an elevation in (VLDL + LDL)-Ch with no significant influence on HDL-Ch. In Donryu rats received a subcutaneous implantation of AH109A cells (an ascites hepatoma line), either 1.2% Met, 1.2% cystine (Cys), or 1.2% Met and 2.5% glycine (Gly) in combination improved a hepatoma-induced hypercholesterolemia and abnormal serum lipoprotein profiles by suppressing a hepatoma-induced increase in (VLDL + LDL)-Ch. From Ch turnover studies in hepatoma-bearing rats, an impaired catabolism of Ch in the liver was suggested to be one cause for the hepatoma-induced elevation in (VLDL + LDL)-Ch. One of the dietary manipulations. met and Gly in combination (Met + Gly), was found to improve the impaired Ch catabolism, this leading to a reduction of the (VLDL + LDL)-Ch level by Met + Gly in hepatoma-bearing rats.

Topics: Amino Acids; Animals; Caseins; Cystine; Dietary Proteins; Glycine; Hypercholesterolemia; Hypothyroidism; Liver Neoplasms, Experimental; Male; Methionine; Rats; Rats, Inbred Strains; Thiouracil

The hypocholesterolemic properties of THD-341, N-(2,6-dimethylphenyl)-delta8-dihydroabietamide, were studied in rats. THD-341 reduced serum cholesterol levels in cholesterol-cholate-fed rats at a concentration of less than 0.001% in the diet or an oral dose of less than 3 mg/kg, once a day. When compared in terms of the 50% inhibitory dose for serum cholesterol elevation (ID 50%, % in diet), THD-341 (0.0008%) was comparable to D-thyroxine (0.0005%), more potent than estradiol (0.003%), and far more potent than clofibrate (0.2%), beta-sitosterol (0.8%), cholestyramine (2%), or nicotinic acid (3%). A daily intravenous injection of THD-341 was also effective (ID 50%: 7 mg/kg). THD-341 reduced serum and liver cholesterol in rats made hypercholesterolemic by 0.3% dietary thiouracil or 0.25% dietary cholate. Liver cholesteriol was more profoundly affected than the serum cholesterol. In normal rats, cholesterol was reduced in liver but not in serum. Its mechanism of action is unknown but the results suggest that THD-341 inhibits cholesterol absorption or re-absorption.

Topics: Abietanes; Animals; Anticholesteremic Agents; Cholesterol, Dietary; Cholic Acids; Diterpenes; Dose-Response Relationship, Drug; Hypercholesterolemia; Liver; Male; Phospholipids; Rats; Thiouracil; Triglycerides

Topics: Androsterone; Animals; Body Weight; Cholesterol; Diet; Estradiol; Hypercholesterolemia; Organ Size; Rats; Testosterone; Thiouracil

Topics: Allografts; Animals; Aorta; Aorta, Abdominal; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Atherosclerosis; Blood Vessels; Cholesterol; Dogs; Hypercholesterolemia; Pathology; Research; Thiouracil; Transplantation, Homologous; Vascular Surgical Procedures

Topics: Hematologic Diseases; Hypercholesterolemia; Lipid Metabolism Disorders; Methylthiouracil; Niacin; Nicotinic Acids; Thiouracil

Topics: Animals; Arteriosclerosis; Diet; Humans; Hypercholesterolemia; Rats; Sitosterols; Steroids; Thiouracil

Topics: Animals; Arteries; Arteriosclerosis; Cholesterol; Diet; Fats; Humans; Hypercholesterolemia; Rats; Sitosterols; Steroids; Thiouracil