Amiodarone and thyroid hormone metabolism in the rat heart

Abstract. The effect of amiodarone on thyroid hormone metabolism in heart, muscle, liver and kidney was investigated. Rats were treated ip with a high (100 mg · kg−1 · day−1) or a low (50 mg · kg−1 · day−1) dose of amiodarone for 10 days. Serum T3 was dose-dependently depressed (mean 30 and 54% of controls, respectively, p<0.01). rT3 was elevated (to 663 and 313% of controls, p<0.01 and 0.05, respectively). Serum T4 was depressed only in the high-dose group (to mean 80%, p<0.05). Tissue concentrations of T3 in the heart and muscle from treated animals did not differ from controls, whereas liver and kidney T3 contents were markedly reduced in both groups (p<0.05). Heart T4 and rT3 were elevated to about 200% of controls (p<0.01 and 0.05, respectively). The same pattern was observed in the other tissues. Iodothyronine-5'-monodeiodinase activity was significantly depressed in all tissues; heart: 32 and 28% of controls (p<0.05); muscle: 36 and 49% (p<0.01); liver: 11 and 13% (p<0.01); kidney: 22 and 28% (p<0.01), respectively. In conclusion, amiodarone depresses iodothyronine-5'-monodeiodinase activity in the heart, muscle, liver and kidney in a dose-dependent manner, resulting in lowered T3 concentrations in the liver and kidney, whereas no reduction of tissue T3 content is observed in the heart and muscle. This may indicate that T3 from plasma may cross the cardiac sarcolemma without hindrance.

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Characterization of Human Iodothyronine Sulfotransferases1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.4.5590 ◽

1999 ◽

Vol 84 (4) ◽

pp. 1357-1364 ◽

Cited By ~ 3

Author(s):

Monique H. A. Kester ◽

Ellen Kaptein ◽

Thirza J. Roest ◽

Caren H. van Dijk ◽

Dick Tibboel ◽

...

Keyword(s):

Thyroid Hormone ◽

Human Liver ◽

Type I ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Iodothyronine Deiodinase ◽

Liver Cytosol ◽

Thyroid Hormone Metabolism ◽

Liver And Kidney ◽

Phenol Sulfotransferase

Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is known about which human sulfotransferase isoenzymes are involved. We have investigated the sulfation of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3′-diiodothyronine (3,3′-T2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively. In all cases, the substrate preference was 3,3′-T2 >> rT3 > T3 > T4. The apparent Km values of 3,3′-T2 and T3 [at 50 μmol/L 3′-phosphoadenosine-5′-phosphosulfate (PAPS)] were 1.02 and 54.9μ mol/L for liver cytosol, 0.64 and 27.8 μmol/L for kidney cytosol, 0.14 and 29.1 μmol/L for SULT1A1, and 33 and 112 μmol/L for SULT1A3, respectively. The apparent Km of PAPS (at 0.1μ mol/L 3,3′-T2) was 6.0 μmol/L for liver cytosol, 9.0μ mol/L for kidney cytosol, 0.65 μmol/L for SULT1A1, and 2.7μ mol/L for SULT1A3. The sulfation of 3,3′-T2 was inhibited by the other iodothyronines in a concentration-dependent manner. The inhibition profiles of the 3,3′-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 μmol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate similar substrate specificities for iodothyronine sulfation by native human liver and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney.

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Mitogenic effects of thyroxine and TRH on thyrotrophs and somatotrophs of the anterior pituitary gland in thyroidectomized rats

Journal of Endocrinology ◽

10.1677/joe.0.1540149 ◽

1997 ◽

Vol 154 (1) ◽

pp. 149-153 ◽

Cited By ~ 10

Author(s):

A Quintanar-Stephano ◽

C Valverde-R

Keyword(s):

Thyroid Hormone ◽

Synergistic Effect ◽

Proliferative Response ◽

Periodic Acid ◽

Male Rats ◽

High Dose ◽

Dependent Manner ◽

Simultaneous Administration ◽

Mitotic Figures ◽

Dose Dependent

Abstract The question of whether thyroxine (T4) and TRH have a mitogenic effect on pituitary thyrotrophs and somatotrophs in thyroidectomized rats was investigated. Mitoses were counted in hematoxylin–eosin-stained or periodic acid–Schiff–hematoxylin-stained pituitary slides or immunostained for TSH or GH using male rats thyroidectomized for 5 months. Ten days before they were killed groups of rats were injected with different doses of T4 (0·5, 3 or 10 μg i.m. every second day for 10 days), TRH alone (100 ng s.c. three times a day for 10 days), or T4 plus TRH (same doses as above). Mitoses (stopped with colchicine) were counted in 1 mm2 areas at a magnification of × 1000. In thyroidectomized rats, mitoses were not significantly increased and treatment with TRH or 0·5 μg T4 alone in thyroidectomized rats did not affect mitotic counts. In thyroidectomized rats treated with higher doses of T4, mitoses were increased in a dose-dependent fashion. Simultaneous administration of TRH and T4 had a significant synergistic effect on pituitary mitoses in a T4 dose-dependent manner. The treatments also had differential effects on the relative percentages of cellular types in mitosis. Thus, 60% somatotrophs and 12·5% thyrotrophs were found in the euthyroid group. In thyroidectomized and thyroidectomized plus TRH groups, no somatotrophs in mitosis were seen, while thyrotrophs were 28·5% and 33·3% respectively. In thyroidectomized rats treated with low doses of T4, somatotrophs and thyrotrophs in mitosis increased to 38·4% and 80% respectively and, with simultaneous administration of a low dose of T4 plus TRH, although less effective than T4 alone, mitosis increased in somatotrophs and thyrotrophs to 11·1% and 54·5% respectively. A high dose of T4 alone did not increase the mitotic figures in somatotrophs (38·8%), while it diminished the percentage of thyrotrophs to 25%. The administration of high doses of T4 plus TRH had an opposite effect on the mitotic figures of somatotrophs and thyrotrophs and thus the percentage of somatotrophs increased to 50% while thyrotrophs decreased to 5·5%. Ten days of treatment with T4 were insufficient to reverse the histology to euthyroidism. It can be concluded that in long-standing hypothyroidism: (1) thyroid hormone replacement elicits a dose-dependent and differential proliferative response on pituitary thyrotrophs and somatotrophs, (2) TRH is devoid of mitogenic effects when administered alone and (3) the proliferative response of somatotrophs to T4 is enhanced by its co-administration with TRH, suggesting a permissive and/or synergistic effect of the thyroid hormone and TRH. Journal of Endocrinology (1997) 154, 149–153

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Altered chicken thyroid hormone metabolism with chronic GH enhancement in vivo: consequences for skeletal muscle growth

Journal of Endocrinology ◽

10.1677/joe.0.1660609 ◽

2000 ◽

Vol 166 (3) ◽

pp. 609-620 ◽

Cited By ~ 25

Author(s):

R Vasilatos-Younken ◽

Y Zhou ◽

X Wang ◽

JP McMurtry ◽

RW Rosebrough ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Body Weight ◽

Thyroid Hormone ◽

Muscle Growth ◽

Somatic Growth ◽

Hormone Metabolism ◽

Thyroid Hormone Metabolism ◽

Igf I ◽

Dose Dependent

In contrast to most vertebrates, GH reportedly has no effect upon somatic growth of the chicken. However, previous studies employed only one to two dosages of the hormone, and limited evidence exists of a hyperthyroid response that may confound its anabolic potential. This study evaluated the effects of 0, 10, 50, 100 and 200 microgram/kg body weight per day chicken GH (cGH) (0-200 GH) infused i.v. for 7 days in a pulsatile pattern to immature, growing broiler chickens (9-10 birds/dosage). Comprehensive profiles of thyroid hormone metabolism and measures of somatic growth were obtained. Overall (average) body weight gain was reduced 25% by GH, with a curvilinear, dose-dependent decrease in skeletal (breast) muscle mass that was maximal (12%) at 100 GH. This profile mirrored GH dose-dependent decreases in hepatic type III deiodinase (DIII) activity and increases in plasma tri-iodothyronine (T(3)), with bot! h also maximal (74 and 108% respectively) at 100 GH. No effect on type I deiodinase was observed. At the maximally effective dosage, hepatic DIII gene expression was reduced 44% versus controls. Despite dose-dependent, fold-increases in hepatic IGF-I protein content, circulating IGF-I was not altered with GH infusion, suggesting impairment of hepatic IGF-I release. Significant, GH dose-dependent increases in plasma non-esterified fatty acid and glucose, and overall decreases in triacylglycerides were also observed. At 200 GH, feed intake was significantly reduced (19%; P<0.05) versus controls; however, additional control birds pair-fed to this level did not exhibit any responses observed for GH-treated birds. The results of this study support a pathway by which GH impacts on thyroid hormone metabolism beginning at a pretranslational level, with reduced hepatic DIII gene expression, translating to reduced protein (enzyme) ex! pression, and reflected in a reduced level of peripheral T(3)-degrading activity. This contributes to decreased conversion of T(3) to its inactive form, thereby elevating circulating T(3) levels. The hyper-T(3) state leads to reduced net skeletal muscle deposition, and may impair release of GH-enhanced, hepatic IGF-I. In conclusion, GH has significant biological effects in the chicken, but profound metabolic actions predominate that may confound positive, IGF-I-mediated skeletal muscle growth.

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A novel mouse model to study the importance of the liver for thyroid hormone metabolism

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2005-862993 ◽

2005 ◽

Vol 113 (S 1) ◽

Author(s):

F Streckfuß ◽

U Schweizer ◽

L Schomburg ◽

J Köhrle

Keyword(s):

Thyroid Hormone ◽

Mouse Model ◽

Hormone Metabolism ◽

Thyroid Hormone Metabolism

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Thyroid Hormone Metabolism and Action in the Brain and Pituitary

Acta Medica Austriaca ◽

10.1046/j.1563-2571.2000.00101.x ◽

2000 ◽

Vol 27 (1) ◽

pp. 1-7 ◽

Cited By ~ 23

Author(s):

J. Kohrle

Keyword(s):

Thyroid Hormone ◽

Hormone Metabolism ◽

Thyroid Hormone Metabolism ◽

The Brain

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High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential

Nutrients ◽

10.3390/nu11091981 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1981 ◽

Cited By ~ 9

Author(s):

Qiufen Mo ◽

Aikun Fu ◽

Lingli Deng ◽

Minjie Zhao ◽

Yang Li ◽

...

Keyword(s):

Lipid Metabolism ◽

Systemic Inflammation ◽

Body Weight Gain ◽

High Dose ◽

Dependent Manner ◽

Glucose And Lipid Metabolism ◽

Glycerol Monolaurate ◽

Indigenous Microbiota ◽

Anti Inflammatory ◽

Dose Dependent

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

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Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

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Concentration-Dependent Antioxidant/Pro-Oxidant Activity of Ascorbic Acid in Chickens

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/v10046-012-0018-8 ◽

2012 ◽

Vol 66 (6) ◽

pp. 256-260

Author(s):

Nadežda Berzina ◽

Jurijs Markovs ◽

Mirdza Apsīte ◽

Svetlana Vasiļjeva ◽

Galina Smirnova ◽

...

Keyword(s):

Oxidative Stress ◽

Ascorbic Acid ◽

Cadmium Concentration ◽

Dehydroascorbic Acid ◽

Cadmium Accumulation ◽

Suppressive Effect ◽

High Dose ◽

Dependent Manner ◽

Treatment Groups ◽

Liver And Kidney

The effects of ascorbic acid supplementation on biomarkers of oxidative stress, cadmium accumulation in organs, immune system activity and kidney function in chickens were investigated. The treatment groups of chickens were fed either plain diet or diet supplemented with ascorbic acid at 100, 500, 1000 and 2000 mg/kg for four weeks. Liver and kidney tissues were assayed for cadmium concentration, and the hepatic levels of ascorbic acid and dehydroascorbic acid (DHAA; the oxidised form), malondialdehyde, glutathione, activity of glutathione peroxidase, blood serum uric acid, creatinine, lysozyme and circulating immune complexes were measured. Supplementation with a high dose of ascorbic acid (1000 and 2000 mg/kg in the diet) caused an imbalance between pro-oxidative and antioxidative activities, and induced a suppressive effect on innate immunity. The results suggest that oxidative stress compromises renal function. We observed that ascorbic acid increased cadmium accumulation in a dose-dependent manner.

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