Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid
| Autor: | Colin Howes, Jong M. Wasvary, Zouhair F. Stephan, Steele Ronald Edward, E.C. Yurachek, Robin Sharif |
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| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Cholic Acid Cardiovascular System Biochemistry chemistry.chemical_compound Internal medicine medicine Animals Potency Euthyroid ED50 Cell Nucleus Pharmacology Receptors Thyroid Hormone Triiodothyronine Dose-Response Relationship Drug Cholesterol Anticholesteremic Agents Cholic acid Cholic Acids Rats Inbred Strains Rats Thyroxine Dose–response relationship Endocrinology Liver chemistry Toxicity |
| Zdroj: | Biochemical Pharmacology. 43:1969-1974 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(92)90640-5 |
| Popis: | This study was designed to determine whether the conjugation product of L-T3 with cholic acid would result in a liver-targeted compound (CGH 509A) with hypocholesterolemic (HC) activity significantly dissociable from cardiovascular (CV) and thyroxine-suppressing (TS) effects normally observed with thyroid hormone. Evaluation of HC activity in lipemic rats showed that CGH 509A was 6 times less potent than L-T3 with ED25 values estimated at 150 and 25 nmol/kg, respectively. CV function measured as changes in atrial rate, atrial tension and heart weight was determined in euthyroid rats. CGH 509A was at least 64 times less cardio-stimulant than L-T3 with minimum effective doses estimated at 2350 and 37 nmol/kg, respectively. TS activity was assessed in euthyroid rats as the potency of any compound to reduce plasma T4 levels. CGH 509A was 50 times less potent than-L-T3 with ED50 values estimated at 900 and 18 nmol/kg, respectively. From these results, it is clear that, while L-T3 was equally potent on HC, CV and TS activities, the HC potency of CGH 509A was at least 15 and 6 times greater than its CV and TS potencies, respectively. |
| Databáze: | OpenAIRE |
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