RESUMO
In view of the traditional belief that Acacia nilotica ssp adansonii (AN) can stimulate milk production in lactating women, experiments were performed to determine the effect of an aqueous extract of AN on milk production in rats. Female rats that received oral doses of aqueous extract of this plant during their first lactation produced about 59% more milk than controls (P<0.01). Pup weight gain was also significantly higher than that in the control group. A lower dose, comparable to that used by women to improve their milk yield, led to about 33% more milk with the same growth rate for pups as that in the high-dose group. The extract of AN was found to stimulate the synthesis and release of prolactin (PRL) significantly (P<0.05). In addition, the mammary glands of oestrogen-primed rats treated with the extract showed clear lobuloalveolar development with milk secretion. This study demonstrates that the aqueous extract of AN can stimulate milk production and PRL release in the female rat and could consequently have the properties claimed for lactating women.
Assuntos
Acacia , Lactação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prolactina/sangue , Administração Oral , Animais , Animais Recém-Nascidos , Bromocriptina/farmacologia , Feminino , Antagonistas de Hormônios/farmacologia , Injeções Intramusculares , Injeções Intravenosas , Glândulas Mamárias Animais/anatomia & histologia , Glândulas Mamárias Animais/efeitos dos fármacos , Hipófise/química , Prolactina/análise , Prolactina/antagonistas & inibidores , Ratos , Ratos Wistar , Aumento de PesoRESUMO
OBJECTIVE: Natural flavonoids (plant pigments) have been shown to inhibit thyroid peroxidase (TPO) in vitro and the growth of thyroid cancer cell lines. We have studied the role of flavonoids on the iodide transport and the growth of the human follicular thyroid cancer cell line (FTC133) which was stably transfected with the human Na(+)/I(-) symporter (hNIS). DESIGN AND METHODS: Cells were treated with flavonoids (0.5-50 microM) for 0, 2, 4 and 6 days; (125)I content and (125)I efflux of the cells and DNA content were measured. RESULTS: Cell growth was inhibited significantly at day 6 by most flavonoids. Eight out of ten flavonoids decreased the (125)I content of the cells at day 4. Morin did not influence the (125)I content of the cells and, surprisingly, myricetin increased the (125)I content of the cells. Kaempferol, apigenin, luteolin and F21388 decreased NIS mRNA expression after 15, 29 and 48 h; after 96 h NIS mRNA returned to normal. CONCLUSION: As TPO is not present in this cell line, the effects of the flavonoids on the iodide uptake are not related to organification. Myricetin was the only flavonoid studied that increased the influx and decreased the efflux of iodide. The effect of myricetin (decreased growth and increased retention of iodide) can be of therapeutic value in the radioiodide treatment of thyroid carcinoma.
Assuntos
Adenocarcinoma Folicular , Flavonoides/farmacologia , Iodetos/metabolismo , Simportadores/genética , Neoplasias da Glândula Tireoide , Transporte Biológico/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/fisiologia , Humanos , Radioisótopos do Iodo , RNA Mensageiro/análise , Simportadores/metabolismo , TransfecçãoRESUMO
UNLABELLED: The most potent natural plant-derived compounds that can affect thyroid function, thyroid hormone secretion and availability to tissues is the group of flavonoids, i.e. plant pigments. They are present in our daily food, such as vegetables, fruits, grains, nuts, wine, and tea. Epidemiological studies suggest beneficial effects on health of flavonoids, which are commonly attributed to their activity as antioxidants. Experimental studies in vitro, however, showed inhibition of organification in thyroid cells and follicles by several flavonoids. Studies in vivo and vitro with synthetic and natural flavonoids showed displacement of T4 from transthyretin leading to disturbances in thyroid hormone availability in tissues. Radioactive labeled flavonoids appeared to be eliminated rapidly from the body mainly through excretion in the feces. In pregnant rats synthetic flavonoids cross the placenta and accumulate in the fetal compartment, including the fetal brain. Therefore, a high intake of flavonoids is contraindicated. IN CONCLUSION: flavonoids show strong interference with many aspects of thyroid hormone synthesis and availability.
Assuntos
Flavonoides/farmacologia , Doenças da Glândula Tireoide/metabolismo , Animais , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Feminino , Feto/metabolismo , Flavonoides/efeitos adversos , Flavonoides/metabolismo , Humanos , Troca Materno-Fetal , Gravidez , Ratos , Hormônios Tireóideos/metabolismoRESUMO
Flavonoids have inhibiting effects on the proliferation of cancer cells, including thyroidal ones. In the treatment of thyroid cancer the uptake of iodide is essential. Flavonoids are known to interfere with iodide organification in vitro, and to cause goiter. The influence of flavonoids on iodine metabolism was studied in a human thyroid cancer cell line (FTC-133) transfected with the human sodium/iodide transporter (NIS). All flavonoids inhibited growth, and iodide uptake was decreased in most cells. NIS mRNA expression was affected during the early hours after treatment, indicating that these flavonoids can act on NIS. Pendrin mRNA expression did not change after treatment. Only myricetin increased iodide uptake. Apeginin, luteolin, kaempferol and F21388 increased the efflux of iodide, leading to a decreased retention of iodide. Instead myricetin increased the retention of iodide; this could be of use in the radioiodide treatment of thyroid cancer.
Assuntos
Flavonoides/farmacologia , Iodo/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Divisão Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Iodo/farmacocinética , RNA Mensageiro/efeitos dos fármacos , Simportadores/efeitos dos fármacos , Simportadores/genética , Simportadores/metabolismo , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Fatores de Tempo , Células Tumorais CultivadasRESUMO
Uptake of iodide is a prerequisite for radioiodide therapy in thyroid cancer. However, loss of iodide uptake is frequently observed in metastasized thyroid cancer, which may be explained by diminished expression of the human sodium-iodide symporter (hNIS). We studied whether transfection of hNIS into the hNIS-deficient follicular thyroid carcinoma cell line FTC133 restores the in vivo iodide accumulation in xenografted tumors and their susceptibility to radioiodide therapy. In addition, the effects of low-iodide diets and thyroid ablation on iodide kinetics were investigated. Tumors were established in nude mice injected with the hNIS-transfected cell line FTC133-NIS30 and the empty vector transfected cell line FTC133-V4 as a control. Tumors derived from FTC133-NIS30 in mice on a normal diet revealed a high peak iodide accumulation (17.4% of administered activity, measured with an external probe) as compared with FTC133-V4 (4.6%). Half-life in FTC133-NIS30 tumors was 3.8 h. In mice kept on a low-iodide diet, peak activity in FTC133-NIS30 tumors was diminished (8.1%), whereas thyroid iodide accumulation was increased. In thyroid-ablated mice kept on a low-iodide diet, half-life of radioiodide was increased considerably (26.3 h), leading to a much higher area under the time-radioactivity curve than in FTC133-NIS30 tumors in mice on a normal diet without thyroid ablation. Experimental radioiodide therapy with 2 mCi (74 MBq) in thyroid-ablated nude mice, kept on a low-iodide diet, postponed tumor development (4 wk after therapy, one of seven animals revealed tumor vs. five of six animals without therapy). However, 9 wk after therapy, tumors had developed in four of the seven animals. The calculated tumor dose was 32.2 Gy. We conclude that hNIS transfection into a hNIS-defective thyroid carcinoma cell line restores the in vivo iodide accumulation. The unfavorable iodide kinetic characteristics (short half-life) can be partially improved by conventional conditioning with thyroid ablation and low-iodide diet, leading to postponed tumor development after radioiodide therapy. However, to achieve sufficient radioiodide tumor doses for therapy, further strategies are necessary, aiming at the mechanisms of iodide efflux in particular.