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硫柳汞对大鼠甲状腺激素代谢的影响。

Effect of thimerosal on thyroid hormones metabolism in rats.

作者信息

Pantaleão Thiago U, Ferreira Andrea C F, Santos Maria C S, Figueiredo Álvaro S P, Louzada Ruy A N, Rosenthal Doris, Carvalho Denise P, Corrêa da Costa Vânia M

机构信息

Laboratório de Fisiologia Endócrina Doris RosenthalInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

NUMPEXPólo de Xerém, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Endocr Connect. 2017 Nov;6(8):741-747. doi: 10.1530/EC-17-0220.

Abstract

Mercury seems to exert an inhibitory effect on deiodinases, but there are few studies using Thimerosal (TM) as the mercury source. We aimed to elucidate the effect of TM on thyroid hormones peripheral metabolism. Adult Wistar female rats received 0.25 µg or 250 µg TM/100 g BW, IM, twice a week, for a month. We evaluated serum total T and T, D1 activity using I-rT as tracer, and D2 activity using I-T NADPH oxidase activity was measured by Amplex-red/HRP method and mRNA levels by real time PCR. Serum T was increased and T decreased by the greatest dose of TM. Even though D1 activity in pituitary and kidney was reduced by the highest dose of TM, hepatic D1 activity and D1 mRNA levels remained unchanged. D2 activity was also significantly decreased by the highest dose of TM in all CNS samples tested, except cerebellum, but D2 mRNA was unaltered. mRNA levels of the tested NADPH oxidases were not affected by TM and NADPH oxidase activity was either unaltered or decreased. Our results indicate that TM might directly interact with deiodinases, inhibiting their activity probably by binding to their selenium catalytic site, without changes in enzyme expression.

摘要

汞似乎对脱碘酶有抑制作用,但很少有研究使用硫柳汞(TM)作为汞源。我们旨在阐明TM对甲状腺激素外周代谢的影响。成年雌性Wistar大鼠每周两次肌肉注射0.25μg或250μg TM/100g体重,持续一个月。我们使用I-反式三碘甲状腺原氨酸(I-rT)作为示踪剂评估血清总T和T、D1活性,使用I-甲状腺素(I-T)评估D2活性。通过Amplex-red/HRP法测量NADPH氧化酶活性,通过实时PCR测量mRNA水平。最大剂量的TM使血清T升高而T降低。尽管垂体和肾脏中的D1活性因最高剂量的TM而降低,但肝脏中的D1活性和D1 mRNA水平保持不变。除小脑外,在所有测试的中枢神经系统样本中,最高剂量的TM也使D2活性显著降低,但D2 mRNA未改变。所测试的NADPH氧化酶的mRNA水平不受TM影响,NADPH氧化酶活性要么未改变,要么降低。我们的结果表明,TM可能直接与脱碘酶相互作用,可能通过与它们的硒催化位点结合来抑制其活性,而酶表达没有变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a5b/5670274/9bba17bc4bfb/ec-6-741-g001.jpg

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