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阿托品可拮抗大鼠急性接触商业性毒死蜱所诱发的类似抑郁的行为。

Atropine counteracts the depressive-like behaviour elicited by acute exposure to commercial chlorpyrifos in rats.

机构信息

Pharmaceutical Sciences Graduate Program, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES 29043-900, Brazil.

Biochemistry and Pharmacology Graduate Program, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES 29043-900, Brazil.

出版信息

Neurotoxicol Teratol. 2019 Jan-Feb;71:6-15. doi: 10.1016/j.ntt.2018.11.002. Epub 2018 Nov 17.

Abstract

Acute organophosphate (OP) poisoning induces well-known signs of toxicosis related to acetylcholinesterase (AChE) inhibition. However, the relationship between acute OP poisoning and the onset of psychiatric disorders remains unclear. Thus, we investigated behavioural and biochemical consequences of acute exposure to the OP chlorpyrifos in male rats and also the effectiveness of the antidotes atropine and pralidoxime on reversing these changes. A sub-lethal dose of commercial chlorpyrifos (20 mg/kg, i.p.) elicited signs of acute toxicosis during the first hours after its injection in rats. Twenty-four hours after treatment, this single dose of chlorpyrifos induced a depressive-like behaviour in the rat forced swimming test without impairing locomotor activity. At this time (24 h), chlorpyrifos decreased plasma butyrylcholinesterase (BChE) activity and hippocampal, striatal and prefrontal cortical AChE activity in rats. The behavioural and biochemical consequences of acute chlorpyrifos poisoning do not seem to be long lasting, since 30 days later they were absent. We evaluated whether these behavioural and biochemical consequences of acute chlorpyrifos treatment would be reversed by the antidotes atropine (10 mg/kg i.p.) and/or pralidoxime (40 mg/kg; i.p.) given 1 h after poisoning. Pralidoxime partially reactivated the AChE activity in the prefrontal cortex, but not in the hippocampus and striatum. Atropine attenuated the depressive-like behaviour induced by chlorpyrifos in rats. Our results suggest that acute chlorpyrifos poisoning induces a transient depressive-like behaviour possible related to hippocampal AChE inhibition. They suggest that treatment with atropine and pralidoxime seems to be insufficient to counteract all the effects of OP acute poisoning, at least in rats.

摘要

急性有机磷(OP)中毒会引起与乙酰胆碱酯酶(AChE)抑制相关的中毒症状。然而,急性 OP 中毒与精神障碍发病之间的关系尚不清楚。因此,我们研究了雄性大鼠急性暴露于 OP 毒死蜱的行为和生化后果,以及抗毒剂阿托品和氯解磷定逆转这些变化的效果。商业毒死蜱(20mg/kg,ip)的亚致死剂量在注射后数小时内引发大鼠急性中毒症状。治疗后 24 小时,单次氯解磷定剂量可引起大鼠强迫游泳试验中的抑郁样行为,而不影响运动活动。在这个时间点(24 小时),氯解磷定降低了大鼠血浆丁酰胆碱酯酶(BChE)活性以及海马、纹状体和前额皮质 AChE 活性。急性氯解磷定中毒的行为和生化后果似乎不会持续很长时间,因为 30 天后它们就消失了。我们评估了急性氯解磷定治疗后的这些行为和生化后果是否可以通过在中毒后 1 小时给予的解毒剂阿托品(10mg/kg,ip)和/或氯解磷定(40mg/kg,ip)逆转。氯解磷定部分恢复了前额皮质中的 AChE 活性,但没有恢复海马和纹状体中的 AChE 活性。阿托品减弱了氯解磷定诱导的大鼠抑郁样行为。我们的研究结果表明,急性氯解磷定中毒可引起短暂的抑郁样行为,可能与海马 AChE 抑制有关。它们表明,阿托品和氯解磷定的治疗似乎不足以对抗 OP 急性中毒的所有影响,至少在大鼠中是如此。

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