propylthiouracil and Hyperlipidemias

Topics: Animals; Anticholesteremic Agents; Antithyroid Agents; Azetidines; Cholesterol; Ezetimibe; Humans; Hyperlipidemias; Hypolipidemic Agents; Propylthiouracil; Rats; Simvastatin

An animal model for clinically observed clofibrate (p-chlorophenoxy isobutyrate, CPIB)-induced toxicity has been tested. It is demonstrated that propylthiouracil-induced hypothyroid-hyperlipidemic chick develops severe toxic manifestations following clofibrate administration. Toxic symptoms are characterized by listlessness, drowziness, and extreme muscular weakness. This is associated with elevation of blood urea nitrogen, creatine phosphokinase, uric acid and glutamic oxaloacetic transaminase. Histological examination of muscle specimen from chicks exhibiting toxic syndrome showed degeneration and vacuolization of muscle fibers. The biochemical and histological changes observed are quite similar to those reported in clinical practice in some patients given clofibrate. It is suggested that this chick model could be used to investigate the biochemical basis of clofibrate toxicity.

Topics: Animals; Chickens; Clofibrate; Hyperlipidemias; Hypothyroidism; Male; Muscles; Propylthiouracil

Circulating levels of insulin, glucagon, thyroid hormones as well as lipid levels were determined in an obese strain of chicken and their lean controls. Hepatic and muscle glycogen and lipids were also measured. Obese birds had higher plasma lipids accompanied by significantly higher insulin and lower glucagon levels compared to lean controls. Hepatic and muscle triglycerides were also higher in obese birds. Plasma T4 level was significantly higher in obese but T3 was not different in the two groups. Results suggest that genetically obese birds have significantly increased insulin/glucagon ratios as previously reported in the PTU induced hypothyroid-obese chicks (Horm. Metab. Res. 12: 51, 1980) and this could have causal relationship to hyperlipidemia and obesity observed in these birds.

Topics: Animals; Chickens; Glucagon; Hyperlipidemias; Hypothyroidism; Insulin; Male; Obesity; Propylthiouracil; Thyroid Hormones

Experimental models for hyper-beta-lipoproteinemia were established in rats and the effects of certain hypolipidemic drugs were studied with these models. In the hyperlipemia induced in rats by feeding a high cholesterol diet, Y-9738 [ethyl 2(4-chlorophenyl)-5-ethoxy-4-oxazoleacetate] produced a dose-dependent reduction of serum cholesterol: such hypolipidemic activity was estimated to be about 7 times as great as that of clofibrate. On the other hand, clofibrate induced hepatomegaly at 100 mg/kg, whereas Y-9738 did not at this dosage, which is about 10 times the effective dose. Hyperlipemia induced by high cholesterol and thiouracil was characterized by increased beta-lipoprotein (heparin-calcium and disc electrophoresis). In this model, Y-9738 showed a dose-dependent lowering effect on beta-lipoprotein cholesterol with a marked decrease in the beta/alpha lipoprotein ratio. A tendency was noted for alpha-lipoprotein to be increased. In contrast, clofibrate exerted no effect on this hyper-beta-lipoproteinemia. These results suggest that the above models may be of value in exploring hyper-beta-lipoproteinemia and that Y-9738 may be more useful than clofibrate in the therapy of hyperlipemia.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Clofibrate; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins, LDL; Male; Oxazoles; Propylthiouracil; Rats; Triglycerides

Topics: Acetates; Animals; Anticholesteremic Agents; Body Weight; Butyrates; Carbon Isotopes; Cholesterol; Hyperlipidemias; Hypolipidemic Agents; Lipids; Liver; Male; Organ Size; Phospholipids; Piperidines; Propylthiouracil; Rats; Triglycerides

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

Topics: Animals; Atherosclerosis; Hyperlipidemias; Propylthiouracil; Rats

Topics: Animals; Bile Acids and Salts; Coronary Disease; Hypercholesterolemia; Hyperlipidemias; Myocardial Infarction; Propylthiouracil; Rats; Salts; Thrombosis