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在CD-1小鼠中,发育阶段接触毒死蜱会导致甲状腺及甲状腺激素水平发生改变,且无其他毒性迹象。

Developmental exposure to chlorpyrifos induces alterations in thyroid and thyroid hormone levels without other toxicity signs in CD-1 mice.

作者信息

De Angelis Simona, Tassinari Roberta, Maranghi Francesca, Eusepi Agostino, Di Virgilio Antonio, Chiarotti Flavia, Ricceri Laura, Venerosi Pesciolini Aldina, Gilardi Enzo, Moracci Gabriele, Calamandrei Gemma, Olivieri Antonella, Mantovani Alberto

机构信息

Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.

出版信息

Toxicol Sci. 2009 Apr;108(2):311-9. doi: 10.1093/toxsci/kfp017. Epub 2009 Feb 3.

Abstract

Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against household pests; these compounds receive an increasing consideration as potential endocrine disrupters. The aim of the present study was to examine the potential short- and long-term effects of CPF on thyroid and adrenal glands in CD1 mice following exposure at dose levels not inducing brain acetyl cholinesterase (AchE) inhibition, during gestational and/or postnatal vulnerable phases. Pregnant dams were treated with 0, 3, 6 mg/kg bw/day of CPF on gestational days 15-18. After delivery, pups were treated subcutaneously on postnatal days (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum thyroxin (T4), thyroid and adrenals histology and histomorphometry were evaluated in dams and in F1 mice. In dams at 6 mg/kg, decreased T4 levels and increased cell height in thyroid were observed, and adrenal histology showed a slightly increased vacuolization in the X-zone. In the F1, short-term morphological modifications (reduced follicular size at PND 2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND 150 with an apparent higher vulnerability of males. For the first time these results indicate that CPF exposure at dose levels not inducing brain AchE inhibition causes thyroid alterations in dams and in F1 CD1 mice. Thyroid may be a sensitive target to CPF developmental exposure possibly leading to long-term effects on thyroid function. Because thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.

摘要

有机磷杀虫剂,如毒死蜱(CPF),广泛用于农业和防治家庭害虫;这些化合物作为潜在的内分泌干扰物受到越来越多的关注。本研究的目的是在妊娠和/或产后易受影响阶段,以不引起脑乙酰胆碱酯酶(AchE)抑制的剂量水平,研究CPF对CD1小鼠甲状腺和肾上腺的潜在短期和长期影响。妊娠母鼠在妊娠第15 - 18天接受0、3、6 mg/kg体重/天的CPF处理。分娩后,幼崽在出生后第11 - 14天皮下注射:0、1、3 mg/kg体重/天的CPF。对母鼠和F1代小鼠的血清甲状腺素(T4)、甲状腺和肾上腺组织学及组织形态计量学进行评估。在6 mg/kg剂量组的母鼠中,观察到T4水平降低,甲状腺细胞高度增加,肾上腺组织学显示X区空泡化略有增加。在F1代中,在出生后第150天发现短期形态学改变(出生后第2天卵泡大小减小)和长期形态学改变(坏死卵泡细胞增加)以及生化改变(血清T4水平降低),雄性小鼠的易感性明显更高。这些结果首次表明,在不引起脑AchE抑制的剂量水平下接触CPF会导致母鼠和F1代CD1小鼠的甲状腺改变。甲状腺可能是CPF发育暴露的敏感靶点,可能导致对甲状腺功能的长期影响。由于甲状腺在哺乳动物发育中起关键作用,这些发现可能与人类相关。

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