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两种农药的发育神经毒性效应:对毒死蜱和西维因的行为及生物分子研究

Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl.

作者信息

Lee Iwa, Eriksson Per, Fredriksson Anders, Buratovic Sonja, Viberg Henrik

机构信息

Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden.

Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden.

出版信息

Toxicol Appl Pharmacol. 2015 Nov 1;288(3):429-38. doi: 10.1016/j.taap.2015.08.014. Epub 2015 Aug 24.

Abstract

In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8-12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.

摘要

近年来,人们已经认识到神经发育障碍,如神经发育迟缓与认知异常的发生率有所增加。接触杀虫剂被怀疑可能是这些疾病的一个成因,因为这些化合物针对害虫的神经系统。由于大脑发育和组成的相似性,这些杀虫剂对人类也可能具有神经毒性。我们研究了两种不同的杀虫剂,毒死蜱和西维因,它们能特异性抑制神经系统中的乙酰胆碱酯酶(AChE)。本研究的目的是调查在大脑快速生长和成熟阶段接触这些杀虫剂时,它们是否会诱发神经毒性作用。本研究结果表明,在出生后第10天给新生小鼠单次口服剂量的毒死蜱(0.1、1.0或5mg/kg体重)或西维因(0.5、5.0或20.0mg/kg体重),这两种化合物都会影响发育中大脑的蛋白质水平,并诱发持续的成年行为和认知障碍。结果还表明,所诱发的发育性神经毒性作用与急性胆碱能过度刺激的经典机制无关,因为AChE抑制水平(8 - 12%)仍低于引起全身毒性的阈值。神经毒性作用更可能是由神经发育紊乱引起的,因为在新生儿大脑发育的关键窗口期接触有机氯、有机磷、拟除虫菊酯和持久性有机污染物等杀虫剂的研究中,也报告了类似的行为神经毒性作用。

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