RESUMEN
Epidemiological studies have demonstrated that n-3 polyunsaturated fatty acid (PUFA) consumption is associated with a reduced risk of atherosclerosis and hyperlipidemia. It is well known that lipid metabolism is also influenced by thyroid hormones. The aim of our study was to test whether n-3 PUFA supplementation (200 mg/kg of body weight/day for 6 weeks given intragastrically) would affect lipid metabolism in Lewis male rats with altered thyroid status. Euthyroid, hypothyroid, and hyperthyroid status of experimental groups was well defined by plasma levels of triiodothyronine, the activity of liver mitochondrial glycerol-3-phosphate dehydrogenase, and by relative heart weight. Fasting blood glucose levels were significantly higher in the hyperthyroid compared to the euthyroid and hypothyroid rats (5.0±0.2 vs. 3.7±0.4 and 4.4±0.2 mmol/l, respectively). In hyperthyroid animals, the concentration of plasma postprandial triglycerides was also increased compared to euthyroid and hypothyroid rats (0.9±0.1 vs. 0.5±0.1 and 0.4±0.1 mmol/l, respectively). On the other hand, hypothyroidism compared to euthyroid and hyperthyroid status was associated with elevated plasma levels of total cholesterol (2.6±0.2 vs. 1.5±0.1 and 1.6±0.1 mmol/l, respectively), LDL cholesterol (0.9±0.1 vs. 0.4±0.1 and 0.2±0.1 mmol/l, respectively) as well as HDL cholesterol (1.6±0.1 vs. 1.0±0.1 and 1.3±0.1 mmol/l, respectively). Supplementation of n-3 PUFA in the present study did not significantly modify either relative heart weight or glucose and lipid levels in any thyroid status.
Asunto(s)
Ácidos Grasos Omega-3/metabolismo , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Metabolismo de los Lípidos , Animales , Colesterol/metabolismo , Suplementos Dietéticos/análisis , Ácidos Grasos Omega-3/administración & dosificación , Glicerolfosfato Deshidrogenasa/metabolismo , Humanos , Hipertiroidismo/enzimología , Hipotiroidismo/enzimología , Hígado/metabolismo , Masculino , Mitocondrias/enzimología , Mitocondrias/metabolismo , Ratas , Ratas Endogámicas Lew , Hormonas Tiroideas/metabolismoRESUMEN
Differentiation and metabolism of adipose tissue are modulated by thyroid hormones (THs), but relatively little is known about the metabolism of THs in this tissue. Expression of the genes for type I iodothyronine 5'-deiodinase (D1), leptin (LEP) and stearoyl-CoA desaturase 1 (SCD-1) was evaluated in omental (OM) and subcutaneous (SC) fat using a cohort of 70 humans. Activities of iodothyronine deiodinases (D1, D2 and D3) were assessed in a randomly selected subpopulation of 19 subjects. D1 expression was upregulated in both OM (P=0.011) and SC (P=0.003) fat of obese subjects. Concomitantly, OM (P=0.002) and SC (P=0.028) LEP expression were increased in obesity, associated with both D1 mRNA (r=0.315, P=0.014) and activity (r=0.647, P=0.023) and inversely related to SCD-1 (r=-0.266, P=0.034) expression in SC fat. Also D1 (but not D2 and D3) activity was increased in OM (â¼fourfold, P=0.010) and SC (â¼eightfold, P=0.004) fat of obese when compared with non-obese subjects and correlated in both OM (r=0.528, P=0.036) and SC (r=0.749, P=0.005) fat with body mass index. Our results document increased D1 gene expression and activity in adipose tissue of obese humans and suggest a role of 3,5,3'-triiodo-L-thyronine formed by D1 in response to leptin in the modulation of adipose tissue metabolism.
Asunto(s)
Tejido Adiposo Blanco/metabolismo , Yoduro Peroxidasa/metabolismo , Leptina/metabolismo , Obesidad/enzimología , Receptores alfa de Hormona Tiroidea/metabolismo , Índice de Masa Corporal , Diferenciación Celular/genética , Estudios de Cohortes , Estudios Transversales , Regulación hacia Abajo , Femenino , Regulación Enzimológica de la Expresión Génica , Humanos , Yoduro Peroxidasa/genética , Leptina/genética , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Receptores alfa de Hormona Tiroidea/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Adipose tissue is an important target for thyroid hormones (TH). However, the metabolism of TH in white adipose tissue is poorly characterized. Our objective was to describe possible changes in activities of TH-metabolizing enzymes in white adipose tissue, and the role of TH metabolism in the tissue during obesogenic treatment, caloric restriction and in response to leptin in mice. Activity of type I iodothyronine 5'-deiodinase (D1) in white fat was stimulated by a high-fat diet, which also increased plasma leptin levels, while brown adipose tissue D1 activity did not change. Caloric restriction decreased the activity of D1 in white fat (but not in the liver), reduced leptin levels, and increased the expression of stearoyl CoA desaturase 1 (SCD-1), a marker and mediator of the effect of leptin on tissue metabolism. Leptin injections increased D1 activity and down-regulated SCD-1 in white fat. Our results demonstrate changes in D1 activity in white adipose tissue under the conditions of changing adiposity, and a stimulatory effect of leptin on D1 activity in the tissue. These results suggest a functional role for D1 in white adipose tissue, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue.
Asunto(s)
Tejido Adiposo Blanco/enzimología , Fenómenos Fisiológicos Nutricionales de los Animales , Restricción Calórica , Yoduro Peroxidasa/metabolismo , Leptina/metabolismo , Obesidad/enzimología , Tejido Adiposo Pardo/enzimología , Tejido Adiposo Pardo/fisiopatología , Tejido Adiposo Blanco/fisiopatología , Animales , Modelos Animales de Enfermedad , Regulación Enzimológica de la Expresión Génica , Inyecciones Subcutáneas , Yoduro Peroxidasa/genética , Leptina/administración & dosificación , Leptina/genética , Ratones , Ratones Endogámicos C57BL , Obesidad/fisiopatología , ARN Mensajero/metabolismo , Proteínas Recombinantes/metabolismo , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismo , Hormonas Tiroideas/metabolismoRESUMEN
Red palm oil (RPO) is a rich natural source of antioxidant vitamins, namely carotenes, tocopherols and tocotrienols. However, it contains approximately 50 % saturated fatty acids the regular consumption of which could negatively modify lipid profile. The aim of our study was to test whether 7 weeks of RPO supplementation (1 g/kg body weight/day) would affect blood glucose and lipid metabolism in adult male Wistar rats with altered thyroid status. We induced hypothyroidism and hyperthyroidism in rats by oral administration of either methimazole or mixture of thyroid hormones. Different thyroid status (EU - euthyroid, HY - hypothyroid and HT - hyperthyroid) was characterized by different serum thyroid hormones levels (total and free thyroxine and triiodothyronine), changes in the activity of a marker enzyme of thyroid status - liver mitochondrial glycerol-3-phosphate dehydrogenase, and altered absolute and relative heart weights. Fasting blood glucose levels were higher in HT rats in comparison with EU and HY rats, but the changes caused by RPO supplementation were not significant. The achievement of the HY status significantly increased serum levels of total cholesterol, as well as with high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol: 2.43+/-0.15, 1.48+/-0.09, 0.89+/-0.08 mmol/l, compared to EU: 1.14+/-0.06, 0.77+/-0.06, 0.34+/-0.05 mmol/l and HT: 1.01+/-0.06, 0.69+/-0.04, 0.20+/-0.03 mmol/l, respectively. RPO supplementation did not increase significantly levels of blood lipids but tended to increase glutathione levels in the liver. In conclusion, RPO supplementation did not induce the presumed deterioration of glucose and lipid metabolism in rats with three well-characterized alterations in thyroid status.
Asunto(s)
Glucemia/metabolismo , Suplementos Dietéticos , Lípidos/sangre , Aceite de Palma/farmacología , Glándula Tiroides/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Glutatión/metabolismo , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Hormonas Tiroideas/sangreRESUMEN
Thyroid hormones are powerful modulators of heart function and susceptibility to arrhythmias via both genomic and non-genomic actions. We aimed to explore expression of electrical coupling protein connexin-43 (Cx43) in the heart of rats with altered thyroid status and impact of omega-3 polyunsaturated fatty acids (omega-3) supplementation. Adult male Lewis rats were divided into following six groups: euthyroid controls, hyperthyroid (treated with T(3)) and hypothyroid (treated with methimazol) with or without six-weeks lasting supplementation with omega-3 (20 mg/100 g/day). Left and right ventricles, septum and atria were used for immunoblotting of Cx43 and protein kinase C (PKC). Total expression of Cx43 and its phosphorylated forms were significantly increased in all heart regions of hypothyroid rats compared to euthyroid controls. In contrast, the total levels of Cx43 and its functional phosphorylated forms were decreased in atria and left ventricle of hyperthyroid rats. In parallel, the expression of PKC epsilon that phosphorylates Cx43, at serine 368, was increased in hypothyroid but decreased in hyperthyroid rat hearts. Omega-3 intake did not significantly affect either Cx43 or PKC epsilon alterations. In conclusion, there is an inverse relationship between expression of cardiac Cx43 and the levels of circulating thyroid hormones. It appears that increased propensity of hyperthyroid while decreased of hypothyroid individuals to malignant arrhythmias may be in part attributed to the changes in myocardial Cx43.
Asunto(s)
Conexina 43/metabolismo , Ácidos Grasos Omega-3/farmacología , Corazón/efectos de los fármacos , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Proteína Quinasa C/metabolismo , Animales , Suplementos Dietéticos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Miocardio/enzimología , Fosforilación , Distribución Aleatoria , Ratas Endogámicas Lew , Hormonas Tiroideas/sangreRESUMEN
Differentiation and biogenesis of mitochondria in brown adipose tissue (BAT) was studied in situ and in cell culture by Western blotting, enzyme activity measurements, [35S]methionine incorporation and immunofluorescence microscopy. In different rodent species the perinatal development of BAT thermogenic function resulted from the formation of thermogenic mitochondria which replaced the preexisting nonthermogenic mitochondria. Their biogenesis was characterized by the sudden appearance and rapid increase of the uncoupling protein (UCP), increase of cytochrome oxidase (COX) and decrease of H(+)-ATPase. In primary cell culture, differentiation of precursor cells from mouse BAT to typical multilocular adipocytes was accompanied by increasing content of COX and H(+)-ATPase. A selective synthesis of UCP was induced by activation of beta-adrenergic receptors or by elevated levels of cellular cAMP. UCP was quantitatively incorporated into mitochondria and within 24 h after stimulation reached near physiological concentration. Both in situ and in cell culture, the conditions enabling the expression of UCP gene were accompanied by activation of intracellular thyroxine 5'-deiodinase.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Mitocondrias/metabolismo , ATPasas de Translocación de Protón/metabolismo , Desacopladores/metabolismo , Tejido Adiposo Pardo/citología , Tejido Adiposo Pardo/enzimología , Animales , Regulación de la Temperatura Corporal , Diferenciación Celular , Células Cultivadas , Cricetinae , Yoduro Peroxidasa/metabolismo , Mesocricetus , Ratones , Ratones Endogámicos BALB C , Microscopía Fluorescente , Perinatología , Ratas , Ratas EndogámicasRESUMEN
The parallel course of the excretion rates of bromide and sodium ions was demonstrated in adult male and female rats administered simultaneously with potassium 82Br-bromide and 24Na-sodium chloride. The animals were exposed to various intakes of sodium ions accompanied with five different anions: Br-, Cl-, HCO3-, ClO4-, and SCN-. Regardless of the anion accompanying the sodium ion, the excretion rates of 82Br- and 24Na+ ions were proportional to the magnitude of sodium intake in the animals. Hence, we have proved our hypothesis that the biological half-life of bromide depends on the magnitude of sodium intake rather than on the intake of chloride.
Asunto(s)
Bromuros/farmacocinética , Sodio/farmacocinética , Animales , Bromuros/administración & dosificación , Bromuros/orina , Radioisótopos de Bromo , Femenino , Semivida , Masculino , Percloratos/administración & dosificación , Compuestos de Potasio/administración & dosificación , Ratas , Ratas Wistar , Sodio/administración & dosificación , Sodio/orina , Bicarbonato de Sodio/administración & dosificación , Cloruro de Sodio/administración & dosificación , Compuestos de Sodio/administración & dosificación , Radioisótopos de SodioRESUMEN
Brown adipose tissue (BAT) is the major thermogenic organ of the human neonate. To determine whether it is also active in the peripheral conversion of T4 to T3, as shown in several animal species, interscapular BAT from 13 newborns of 25-40 weeks gestational age who survived 4 days, at most, was investigated. BAT was found to contain significant amounts of the mitochondrial uncoupling protein (UCP), the rate-limiting component of heat production. The specific content of UCP increased from 29.4 +/- 3.3 to 62.5 +/- 10.2 pmol/mg protein between 25 and 40 weeks of gestation, respectively, and the UCP/F1-ATPase molar ratio, a sensitive marker of brown fat differentiation, increased similarly. BAT was also found to contain iodothyronine 5'-deiodinase (5'D), which appears to be a type II enzyme, based on high affinity for T4 (Km, 2.9 nmol/L) and insensitivity to propylthiouracil (10% inhibition by 1 nmol/L). 5'D was active by 25 weeks gestation, and the specific activity increased from 116 +/- 15 to 417 +/- 46 fmol/h.mg protein during the period examined. The development of 5'D activity was similar to the changes in UCP content; both exhibited a major increase before 32 weeks gestation. The results indicate that thermogenic function and 5'D activity develop in human BAT rather early, during the first half of the last trimester of gestation. The activities of 5'D in human BAT are comparable with 5'D activities found in animal BAT stimulated during the perinatal period, by cold exposure, or by increased cAMP levels.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Proteínas Portadoras/biosíntesis , Recién Nacido/metabolismo , Yoduro Peroxidasa/biosíntesis , Proteínas de la Membrana/biosíntesis , Tejido Adiposo Pardo/ultraestructura , Factores de Edad , Análisis de Varianza , Animales , Regulación de la Temperatura Corporal , Cricetinae , Complejo IV de Transporte de Electrones/biosíntesis , Femenino , Edad Gestacional , Humanos , Immunoblotting , Canales Iónicos , Masculino , Mesocricetus , Ratones , Ratones Endogámicos BALB C , Mitocondrias/metabolismo , Proteínas Mitocondriales , ATPasas de Translocación de Protón/biosíntesis , Proteína Desacopladora 1RESUMEN
The mRNA levels of ATPase beta, ATPase 6, cytochrome oxidase (COX) VIb and COX I subunits were found to be 2.4-13.8-fold higher in brown adipose tissue (BAT) than in heart, skeletal muscle, brain and liver of mice. The comparison with tissue contents of ATPase and COX revealed that the selective, 5-11-fold reduction of ATPase in BAT is not caused by decreased transcription of ATPase genes. Likewise, the ATPase beta and COX VIb mRNA levels in cultured brown adipocytes were also not influenced by norepinephrine, which activated the expression of the UCP gene by two orders of magnitude. The results indicate that the biosynthesis of mitochondrial ATPase in BAT is post-transcriptionally regulated.
Asunto(s)
Adenosina Trifosfatasas/metabolismo , Tejido Adiposo Pardo/enzimología , Mitocondrias/enzimología , Transcripción Genética , Adenosina Trifosfatasas/genética , Animales , Northern Blotting , Encéfalo/enzimología , Frío , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Expresión Génica , Hígado/enzimología , Ratones , Ratones Endogámicos BALB C , Músculos/enzimología , Miocardio/enzimología , Biosíntesis de Proteínas , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Brown adipocytes differentiated in primary cell culture were found to contain a type II iodothyronine 5'-deiodinase (5'D). Incubation of confluent cells with norepinephrine or dibutyryl-cAMP caused up to 17-fold increase in 5'D activity with a maximum after 8 h. Activation of 5'D required mRNA and protein synthesis and was accompanied by parallel, up to 5.8-fold increase in the amount of mitochondrial uncoupling protein with a maximum after 24 h. Analysis of adrenergic stimulation of 5'D suggested predominant involvement of the beta-receptors and increased intracellular cAMP levels, while the contribution of alpha 1-receptors was small.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Proteínas Portadoras , Yoduro Peroxidasa/biosíntesis , Proteínas de la Membrana/biosíntesis , Tejido Adiposo Pardo/citología , Tejido Adiposo Pardo/efectos de los fármacos , Animales , Bucladesina/farmacología , Células Cultivadas , Colforsina/farmacología , Cicloheximida/farmacología , Dactinomicina/farmacología , Inducción Enzimática , Canales Iónicos , Isoproterenol/farmacología , Cinética , Ratones , Ratones Endogámicos BALB C , Mitocondrias/metabolismo , Proteínas Mitocondriales , Norepinefrina/farmacología , Fenilefrina/farmacología , Prazosina/farmacología , Propranolol/farmacología , Proteína Desacopladora 1RESUMEN
A maleimide spin label strongly inhibits the phosphate/H+ symporter of rat liver mitochondria. While inducing half-maximal inhibition of transport, the spin label reacts preferentially with the SH groups of the carrier, which are at least of two types. One type of SH group is localized close to the surface of the membrane and its environment does not significantly influence the mobility of the probe. The second type of SH group is buried in the membrane, is not accessible to ascorbate or chromium oxalate and its environment greatly restricts the motion of the probe.
Asunto(s)
Proteínas Portadoras/metabolismo , Óxidos N-Cíclicos , Mitocondrias Hepáticas/metabolismo , Marcadores de Spin , Compuestos de Sulfhidrilo/metabolismo , Animales , Sitios de Unión , Fenómenos Químicos , Química , Espectroscopía de Resonancia por Spin del Electrón , Técnicas In Vitro , Membranas Intracelulares/metabolismo , Proteínas de Unión a Fosfato , RatasRESUMEN
The present study employed neuropharmacological and receptor binding protocols to determine if diazepam-sensitive (DS) gamma-aminobutyric acid-A (GABA(A)) receptors in the nucleus tractus solitarius (NTS) participate in autonomic regulation of cardiovascular function. The first set of protocols was designed to determine if GABA(A) receptors in the NTS were functionally modulated by the benzodiazepine agonist, diazepam. Mean arterial pressure and heart rate responses to microinjection of GABAergic substances into the NTS were examined in urethane-anesthetized rats. Microinjection of the GABA(A) agonist isoguvacine into the NTS increased mean arterial pressure and heart rate, and these effects were blocked by the GABA(A) receptor antagonist, bicuculline. Preadministration of diazepam into the NTS potentiated the pressor actions of isoguvacine and had variable effects on heart rate changes. Flumazenil, a benzodiazepine antagonist, blocked the diazepam-induced potentiation of the pressor response to isoguvacine. The second protocol employed receptor autoradiography to examine the presence of DS and diazepam-insensitive (DI) GABA(A) receptors in the NTS. Autoradiography confirmed that DS GABA(A) receptors were present in the NTS; however, no measurable levels of DI GABA(A) receptors were detected. We conclude that GABA(A)-mediated integration of central autonomic control in the NTS is mediated solely by DS GABA(A) receptors.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Encéfalo/fisiología , Diazepam/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Receptores de GABA-A/fisiología , Núcleo Solitario/fisiología , Marcadores de Afinidad , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/farmacología , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiología , Autorradiografía , Azidas/metabolismo , Benzodiazepinas/metabolismo , Diazepam/administración & dosificación , Sinergismo Farmacológico , Agonistas del GABA/farmacología , Ácidos Isonicotínicos/farmacología , Masculino , Microinyecciones , Ratas , Ratas Sprague-Dawley , Receptores de GABA-A/efectos de los fármacos , Núcleo Solitario/efectos de los fármacos , TritioRESUMEN
A significant impact of high bromide levels in the organism of the mother on iodine transfer to the sucklings was established in experiments with female Wistar rats. The observed decrease in iodine transfer to the young through mothers' milk and/or an increase in the bromide concentration in the milk, caused a decrease in body weight of the pups. Enhanced bromide levels also adversely affected the thyroid gland of the young. High bromide intake in the lactating dams caused a decrease in iodide accumulation in the mammary glands, and also an increase in iodide elimination through the kidneys.
Asunto(s)
Animales Lactantes , Bromuros/administración & dosificación , Yodo/farmacocinética , Animales , Femenino , Masculino , Tamaño de los Órganos , Radioinmunoensayo , Ratas , Ratas Wistar , Glándula Tiroides/anatomía & histología , Hormonas Tiroideas/sangreRESUMEN
The present knowledge about the metabolism of bromide with respect to its goitrogenic effects, including some conclusions drawn from our recent research on this subject, is reviewed. Firstly, the biological behavior of bromide ion is compared with that of chloride and iodide. Secondly, the details about distribution and kinetics of bromide ions in the body and in 15 different organs and tissues of the rat are given. Significant correlation between the values of the steady-state concentration of bromide in the respective tissue and of the corresponding biological half-life was found in most tissues examined. A remarkably high concentration of radiobromide was found in the skin, which represents, due to its large mass, the most abundant depot of bromide in the body of the rat. Thirdly, the effects of excessive bromide on the rat thyroid are summarized, along with the interference of exogenous bromide with the whole-body metabolism of iodine. It is suggested that high levels of bromide in the organism of experimental animals can influence their iodine metabolism in two parallel ways: by a decrease in iodide accumulation in the thyroid and skin (and in the mammary glands in lactating dams), and by a rise in iodide excretion by kidneys. By accelerating the renal excretion of iodide, excessive bromide can also influence the pool of exchangeable iodide in the thyroid. Finally, our recent results concerning the influence of high bromide intake in the lactating rat dam on iodine and bromide transfer to the suckling, and the impact of seriously decreased iodine content and increased bromide concentration in mother's milk on the young are discussed. We must state, however, that the virtue of the toxic effects of excessive bromide on the thyroid gland and its interference with the biosynthesis of thyroid hormones, as well as the exact mechanism of bromide interference with postnatal developmental processes remains to be elucidated.
Asunto(s)
Antitiroideos/metabolismo , Bromuros/metabolismo , Yodo/metabolismo , Glándula Tiroides/efectos de los fármacos , Animales , Bromuros/farmacocinética , Bromuros/farmacología , Radioisótopos de Bromo , Cloruros/metabolismo , Humanos , Yodo/deficiencia , Yodo/farmacocinética , Radioisótopos de Yodo , Lactancia , Glándula Tiroides/metabolismo , Recuento Corporal TotalRESUMEN
The biological half-life of bromine in the rat thyroid was determined by measuring the radioactivity of thyroids of animals which continuously received 82Br labelled bromide in their food. The value of this half-life (110 h) is practically the same as the biological half-life of iodine. The rate of establishing the I/Br concentration ratio in the thyroid depends on the biological half-life of bromine. The mechanism of this process depends on the state of iodine supply. When the supply is sufficient, the iodine concentration in the thyroid remains constant, while during iodine deficiency the iodine atoms are replaced by atoms of bromine.
Asunto(s)
Bromo/farmacocinética , Glándula Tiroides/metabolismo , Animales , Semivida , Masculino , Ratas , Ratas WistarRESUMEN
The distribution of 82Br-bromide in 15 different organs and tissues of rats has been determined by high-resolution gamma-ray spectrometry and by the scintillation counting technique at different times after the application of Na 82Br, either by subcutaneous injection or by continuous administration in the drinking water. The amount of 82Br-bromide in the various tissues reached its largest uptake within a few hours, and the concentration ratio of 82Br in the tissues to blood remained practically constant between 8 and 396 h after the application. The whole stomach of rats was the only organ of those investigated that had a larger uptake of 82Br than blood. Contrary to some previous findings, the concentration of radiobromide in the thyroid was found not to exceed that in the blood. A remarkably high concentration of 82Br was found in the skin, which represented, because of its large mass, the most abundant depot of bromide in the body of rats. The demonstrated excretion of bromide was mainly renal, at a rate of approximately 5% of the administered dose per 24 h.
Asunto(s)
Bromuros/farmacocinética , Radioisótopos de Bromo/farmacocinética , Animales , Bromuros/administración & dosificación , Bromuros/sangre , Radioisótopos de Bromo/sangre , Rayos gamma , Masculino , Ratas , Ratas Wistar , Compuestos de Sodio/administración & dosificación , Compuestos de Sodio/farmacocinética , Espectrofotometría , Factores de Tiempo , Distribución TisularRESUMEN
In experiments on rats, a significant influence of an extraordinarily high bromide intake on the whole-body biological half-life of iodine was established. Very high bromide intake (1) decreased the amount of radioiodide accumulated in the thyroid, (2) changed the proportion between the amount of iodine retained in the thyroid and the total amount of absorbed iodine, (3) significantly shortened the biological half-life of iodine in the thyroid from approximately 101 h to 33 h in animals maintained on an iodine-sufficient diet and from 92 h to about 30 h in rats fed a low-iodine diet, and (4) changed the time-course (added a further phase) of iodine elimination from the body. These changes were caused, with high probability, by an increase of iodine elimination by kidneys due to an excess of bromide. The overall picture of iodine elimination in animals fed the low-iodine diet was similar to that in animals maintained on iodine-sufficient diet.
Asunto(s)
Bromuros/metabolismo , Yodo/metabolismo , Animales , Bromuros/administración & dosificación , Dieta , Semivida , Yodo/administración & dosificación , Yodo/deficiencia , Radioisótopos de Yodo , Riñón/metabolismo , Masculino , Ratas , Ratas Wistar , Glándula Tiroides/metabolismoRESUMEN
The effect of a high bromide intake on the kinetics of iodide uptake and elimination in the thyroid and skin of adult male rats was studied. In rats fed a diet with sufficient iodine supply (> 25 microg I/d), the iodide accumulation in the skin predominated during the first hours after 131I iodide application. From this organ, radioiodide was gradually transferred into the thyroid. A high bromide intake (> 150 mg Br-/d) in these animals led to a marked decrease in iodide accumulation, especially by the thyroid, because of an increase in iodide elimination both from the thyroid and from the skin. In rats kept under the conditions of iodine deficiency (< 1 micro I/d), the iodide accumulation in the thyroid, but not in the skin, was markedly increased as a result of a thyrotropic stimulation. The effect of a high bromide intake (> 100 mg Br-/d) in these animals was particularly pronounced because the rates of iodide elimination were most accelerated both from their thyroid and from their skin.
Asunto(s)
Bromuros/administración & dosificación , Yodo/metabolismo , Piel/metabolismo , Glándula Tiroides/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Dieta , Semivida , Yodo/administración & dosificación , Yodo/deficiencia , Radioisótopos de Yodo , Cinética , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Piel/anatomía & histología , Piel/efectos de los fármacos , Glándula Tiroides/anatomía & histología , Glándula Tiroides/efectos de los fármacosRESUMEN
Biological half-lives of bromine in 15 different organs and tissues of the rat, in addition to the whole-body half-life, were determined by measuring the radioactive concentration of 82Br-bromide in samples of tissues collected at the time intervals of 12-396 h from animals that continuously (up to 17 d) received 82Br-labeled bromide in their drinking water. The half-life values, calculated from the experimental data by the method of gradual estimates of the parameters in question with the SPSS statistical program, ranged from 94.3+/-14.6 h in the thyroid gland to 235.0+/-88.9 h in liver. In most of the studied tissues, the biological half-lives of bromine were shorter than in the whole body, in which it equaled 197.8+/-22.2 h. Significant correlation between the values of the steady-state concentration of bromide and of the biological half-life was found for most tissues (except for liver). The steady-state concentrations of 82Br in tissues are probably proportional to the magnitude of bromide space, and, consequently, of chloride space.
Asunto(s)
Bromuros/farmacocinética , Radioisótopos de Bromo/farmacocinética , Animales , Hígado/metabolismo , Masculino , Modelos Estadísticos , Ratas , Ratas Wistar , Glándula Tiroides/metabolismo , Factores de Tiempo , Distribución TisularRESUMEN
We newly elaborated and adapted several radiometric enzyme assays for the determination of activities of the key enzymes engaged in the biosynthesis (thyroid peroxidase, TPO) and metabolic transformations (conjugating enzymes and iodothyronine deiodinases, IDs) of thyroid hormones (THs) in the thyroid gland and in peripheral tissues, especially in white adipose tissue (WAT). We also elaborated novel, reliable radiometric methods for extremely sensitive determination of enzyme activities of IDs of types 1, 2 and 3 in microsomal fractions of different rat and human tissues, as well as in homogenates of cultured mammalian cells. The use of optimized TLC separation of radioactive products from the unconsumed substrates and film-less autoradiography of radiochromatograms, taking advantage of storage phosphor screens, enabled us to determine IDs enzyme activities as low as 10(-18) katals. In studies of the interaction of fluoxetine (Fluox) with the metabolism of THs, we applied adapted radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'-diphospho-glucuronyltransferase (UDP-GT). Fluox is the most frequently used representative of a new group of non-tricyclic antidepressant drugs--selective serotonin re-uptake inhibitors. We used the elaborated assays for quantification the effects of Fluox and for the assessment of the degree of potential induction of rat liver ST and/or UDP-GT enzyme activities by Fluox alone or in combination with T(3). Furthermore, we studied possible changes in IDs activities in murine adipose tissue under the conditions that promoted either tissue hypertrophy (obesogenic treatment) or involution (caloric restriction), and in response to leptin, using our newly developed radiometric enzyme assays for IDs. Our results suggest that deiodinase D1 has a functional role in WAT, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue. Significant positive correlation between specific enzyme activity of D1 in WAT and plasma leptin levels was found. The newly developed and adapted radiometric enzyme assays proved to be very useful tools for studies of factors modulating THs metabolism, not only in model animals but also in clinical studies of human obesity.