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Gestational exposure to paracetamol in rats induces neurofunctional alterations in the progeny.
Neurotoxicology and Teratology ( IF 2.9 ) Pub Date : 2019-10-20 , DOI: 10.1016/j.ntt.2019.106838
Rodrigo Moreno Klein 1 , Camila Rigobello 2 , Camila Borecki Vidigal 1 , Kawane Fabrício Moura 1 , Décio Sabbatini Barbosa 2 , Daniela Cristina Ceccatto Gerardin 1 , Graziela Scalianti Ceravolo 1 , Estefânia Gastaldello Moreira 3
Affiliation  

Paracetamol (PAR) is an over-the-counter medicine used as analgesic or antipyretic by 40-50% of the pregnant women in different countries. Epidemiologic studies have been associating maternal use of PAR with neurodevelopmental disruption and special attention has been given to its potential to increase the odds for neurodevelopmental disorders, such as attention-deficit hyperactive disorder and autism spectrum disorder. Population-based research do not allow the establishment of causal relationships because variable control is weak. We aimed to evaluate the potential of PAR to induce developmental neurotoxicity in rats. Pregnant Wistar rats were gavaged with PAR (350 mg/kg/day) or water from gestational day 6 until delivery. General toxicity endpoints included dams' body weight and food intake as well as pups' body weight until weaning. Behavioral evaluation occurred at post-natal days 10 (nest seeking test), 27 (behavioral stereotypy), 28 (three chamber sociability test and open field) and 29 (hot plate and elevated plus-maze). Moreover, lipid hidroperoxide (LOOH), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were quantified in prefrontal cortex and hippocampus of 22-days-old rats. Gestational exposure to PAR impaired nest seeking behavior, augmented apomorphine-induced behavioral stereotypy and decreased rostral grooming in the elevated plus maze. Exposed female pups presented elevated vertical exploration in the open field test. No alterations were observed in LOOH, GSH or BDNF levels in the prefrontal cortex or hippocampus. Exposure regimen did not affect general toxicity parameters or pups' behavior in the hot plate and sociability tests. These data suggest PAR as a developmental neurotoxicant. Observed alterations may be relevant for neurodevelopmental disorders.

中文翻译:

妊娠大鼠暴露于扑热息痛可诱发后代神经功能改变。

扑热息痛(PAR)是一种非处方药,在不同国家/地区被40-50%的孕妇用作镇痛药或解热药。流行病学研究已将孕产妇使用PAR与神经发育障碍相关联,并特别注意其增加潜在的神经发育障碍(如注意力缺陷多动障碍和自闭症谱系障碍)几率。由于变量控制薄弱,基于人口的研究不允许建立因果关系。我们旨在评估PAR诱导大鼠发育神经毒性的潜力。从妊娠第6天直至分娩,对怀孕的Wistar大鼠进行PAR(350mg / kg /天)或水的灌胃。一般的毒性终点包括大坝的体重和食物摄入量以及断奶前幼崽的体重。行为评估发生在产后第10天(巢巢测试),27天(行为刻板印象),28天(三房社交测试和开放视野)和29天(热板和高迷宫)。此外,对22日龄大鼠的前额叶皮层和海马中的脂质脂质过氧化物(LOOH),还原型谷胱甘肽(GSH)和脑源性神经营养因子(BDNF)水平进行了定量。妊娠期PAR的暴露会损害巢的寻找行为,增加阿扑吗啡诱导的行为刻板印象,并在高架迷宫中减少眼部修饰。裸露的幼崽在野外试验中表现出较高的垂直探测能力。在前额叶皮层或海马中没有观察到LOOH,GSH或BDNF水平的改变。暴露方案不影响一般毒性参数或幼犬在热板和社交性测试中的行为。这些数据表明PAR是一种发育性神经毒剂。观察到的变化可能与神经发育障碍有关。
更新日期:2019-11-01
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