CHRONIC ORAL TOXICITY OF 3, 5, 3'-TRIIODO-4'-ACETYLTHYROFORMIC ACID WITH SPECIAL REFERENCE TO CHOLESTEROLYTIC EFFECTS
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概要
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Though the use of thyroid hormone in the treatment of hypercholesterolemia in the humans received wide acceptance, its practical use is limited by the high incidence of angina attack and by the influence through the augmented rate of basal metabolism. 3, 5, 3'-Triiodothyronine (T<SUB>3</SUB>), 3, 5, 3'-triiodothyroacetic acid (Triac), 3, 5, 3'5'-tetraiodothyroacetic acid (Tetrac) and other possible metabolites of thyroxine were reported to suppress serum cholesterol levels within the range of doses which did not produce concomitant rise in basal metabolic rate (1-4). Through these experiments the evaluation of other derivatives became one of the most attractive projects not only for the clinical but also the experimental studies for attempting to separate the cholesterolytic property from the effect on the basal metabolism by changing the chemical structures. Among them, 3, 5, 3'-triiodothyroformic acid (T<SUB>3</SUB>-F) was reported by Boyd and Oliver (3, 4) as a possible metabolite of thyroxine. Kumaoka <I>et al</I>. (5) demonstrated that 3, 5, 3'-triiodo-4'acetyl-thyroformic acid (TBF-43) produced a moderate cholesterolytic effect without much increase of basal metabolic rate in cases of essential hypertension and myxedema when 10 to 50 mg were prescribed daily. Acute and subacute toxicities of the compound were presented by Aramaki <I>et al</I>. (6) and Kajihara <I>et al</I>. (7). They reported that subacute oral administration of TBF-43 in the daily doses above 40 mg/kg caused a retardation of growth in rats. Furthermore, the autopsy study proved an increase in the weight of the parenchymal organs, especially the heart, kidney and adrenal gland.<BR> The present report deals with the chronic oral toxicities of TBF-43 in the rats and rabbits fed on the standard diet or high-cholesterol diet.
- 公益社団法人 日本薬理学会の論文
著者
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高折 修二
Department of Pharmacology, Faculty of Medicine, Kyoto University
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島本 暉朗
Department of Pharmacology, Faculty of Medicine, Kyoto University
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大隅 義継
Department of Pharmacology, Faculty of Medicine, Kyoto University
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