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Rutin Scavenges Reactive Oxygen Species, Inactivates 5′-Adenosine Monophosphate-Activated Protein Kinase (AMPK) and Increases NIS expression in thyroid PCCL3 Cells.

Rutin Scavenges Reactive Oxygen Species, Inactivates 5′-Adenosine Monophosphate-Activated Protein Kinase (AMPK) and Increases NIS expression in thyroid PCCL3 Cells.
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Gonçalves CFL, Freitas ML, Fortunato RS, Miranda-Alves L, Carvalho DP, Ferreira ACF,


Gonçalves CFL, Freitas ML, Fortunato RS, Miranda-Alves L, Carvalho DP, Ferreira ACF, (click to view)

Gonçalves CFL, Freitas ML, Fortunato RS, Miranda-Alves L, Carvalho DP, Ferreira ACF,

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Thyroid : official journal of the American Thyroid Association 2017 11 21() doi 10.1089/thy.2016.0585

Abstract
BACKGROUND
Thyroid iodide uptake, mediated by the sodium-iodide symporter (NIS), is essential for thyroid hormone synthesis and also for treatment of thyroid diseases, such as thyroid cancer, through radioiodine therapy. Therefore, compounds able to increase thyroid iodide uptake could be clinically useful, and it is of great importance to unravel the mechanisms underlying such effect. We have previously shown that the flavonoid rutin increases thyroid radioiodide uptake in vivo, in rats. Herein, we aimed at studying the mechanisms involved in the stimulatory effect of rutin on iodide uptake.

METHODS
We evaluated iodide uptake, NIS expression and its subcellular distribution, iodide efflux, reactive oxygen species (ROS) levels, and the intracellular pathways involved in NIS regulation in rat thyroid PCCL3 cell line treated with rutin.

RESULTS
Similarly to our previous results found in vivo, rutin also increased radioiodide uptake in PCCL3 cells, which was accompanied by increased NIS expression (at both the mRNA and protein levels) and a reduction of radioiodide efflux. Moreover, our results suggest that rutin could regulate NIS subcellular distribution, leading to higher levels of NIS at the cell membrane. In addition, rutin decreased the levels of intracellular reactive oxygen species, and decreased the phospho-5′-adenosine monophosphate-activated protein kinase (p-AMPK) levels.

CONCLUSIONS
The flavonoid rutin seems to be an important stimulator of radioiodide uptake, acting at multiple levels, an effect that can be due to decreased oxidative stress, reduced AMPK activation, or both. Since thyroid iodide uptake is crucial for effective radioiodine therapy, our results suggest that rutin could be useful as candidate for adjuvant in radioiodine therapy.

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