Background: Liothyronine (LT3) has limited short-term clinical applications, all of which aim at suppressing thyrotropin (TSH) secretion. A more controversial application is chronic administration along with levothyroxine in the treatment of hypothyroidism. Long-term treatment with LT3 is complicated by its unique pharmacokinetics that result in a substantial triiodothyronine (T3) peak in the blood three to four hours after oral dosing. This is a significant problem, given that T3 levels in the blood are normally stable, varying by <10% throughout the day.
Methods: A metal coordinated form of LT3 (Zn[T3][HO])n, known as poly-zinc-liothyronine (PZL), was synthesized and loaded into coated gelatin capsules for delivery to the duodenum where sustained release of T3 from PZL occurs. Male Wistar rats were made hypothyroid by feeding on a low iodine diet and water containing 0.05% methimazole for five to six weeks. Rats were given a capsule containing 24 μg/kg PZL or equimolar amounts of LT3. Blood samples were obtained multiple times from the tail vein during the first 16 hours, and processed for T3 and TSH serum levels. Some animals were treated daily for eight days, and blood samples were collected daily.
Results: Rats given LT3 exhibited the expected serum T3 peak (about fivefold baseline) at 3.5 hours, followed by a rapid decline, with serum levels almost returning to baseline values by 16 hours. In contrast, serum T3 in PZL-treated rats exhibited about a 30% lower T3 peak at nine hours. Furthermore, the plateau time, that is, the time-span during which the serum T3 concentration is at least half of T3 peak, increased from 4.9 to 7.7 hours in LT3- versus PZL-treated rats, respectively. Serum TSH dropped in both groups, but PZL-treated rats exhibited a more gradual decrease, which was delayed by about four hours compared to LT3-treated rats. Chronic treatment with either LT3 or PZL restored growth, lowered serum cholesterol, and stimulated hepatic expression of the Dio1 mRNA and other T3-dependent markers in the central nervous system.
Conclusion: Capsules of PZL given orally restore T3-dependent biological effects while exhibiting a reduced and delayed serum T3 peak after dosing, thus providing a longer period of relatively stable serum T3 levels compared to capsules of LT3.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207055 | PMC |
| http://dx.doi.org/10.1089/thy.2018.0205 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tannic acid coordination assembly enhances the interfacial properties of salted egg white gel particles.
Int J Biol Macromol
December 2024
Cooperative Innovation Center of Industrial Fermentation, Ministry of education & Hubei province, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, China. Electronic address:
Tannic acid (TA) has attracted the attention of researchers as a promising organic ligand capable of forming metal-organic coordination networks with various metal ions at interfaces to impact surface properties. In this study, we innovatively reported a self-assembly method for surface decoration by depositing TA/Fe coatings on the surface of desalted duck egg white nanoparticles (DEWN), further studying the oil/water interfacial properties of the modified particles. The results showed that the ratio and concentration of TA to Fe could modulate interfacial properties.
View Article and Find Full Text PDFScaffolding and Heavy-Atom Effects of Metal Chains Enhanced Tunable Long Persistent Luminescence in Metal-Organic Frameworks.
Inorg Chem
December 2024
Key Laboratory of Chemical Additives for China National Light Industry, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
Metal-organic frameworks (MOFs) with long persistent luminescence (LPL) have attracted extensive research attention due to their potential applications in information encryption, anticounterfeiting technology, and security logic. The strategic combinations of organic phosphor linkers and metal ions lead to tremendous frameworks, which could unveil many undiscovered properties of organics. Here, the synthesis and characterization of a three-dimensional MOF (Cd-MOF) is reported, which demonstrates enhanced blue photoluminescence and a phosphorescent lifetime of 124 ms as compared to the pristine linker (HL) under ambient conditions due to the scaffolding and heavy-atom effects of metal chains in the framework.
View Article and Find Full Text PDFBarriers and Carriers for Transition Metal Homeostasis in Plants.
Plant Commun
December 2024
National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:
Transition metals are a type of metal with high chemical activity and play critical roles in plant growth and development, reproduction and environmental adaptation, as well as for human health. However, the acquisition, transportation and storage of these metals always pose specific challenges due to their nature of high reactivity and poor solubility. In addition, distinct yet interconnected apoplastic and symplastic diffusion barriers impede their movement throughout the plants.
View Article and Find Full Text PDFCopper-coordination driven brain-targeting nanoassembly for efficient glioblastoma multiforme immunotherapy by cuproptosis-mediated tumor immune microenvironment reprogramming.
J Nanobiotechnology
December 2024
Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, the Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, 570102, China.
Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs.
View Article and Find Full Text PDFEnantioselective Synthesis of Chiral β-Amino Phosphorus Derivatives via Nickel-Catalyzed Asymmetric Hydrogenation.
J Am Chem Soc
December 2024
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Compared with chiral β-amino phosphorus compounds, which can be easily derived from natural optically pure α-amino acids, obtaining chiral β-amino phosphorus derivatives remains a challenge. These derivatives, which cannot be derived from chiral natural amino acids, possess unique biological activities or potential catalytic activities. Herein, highly enantioselective hydrogenation for the preparation of chiral β-amino phosphorus derivatives from -β-enamido phosphorus compounds is reported by using a green and low-cost earth-abundant metal nickel catalyst (13 examples of 99% ee).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!