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单种或联合暴露于毒死蜱和氯氰菊酯会引发大鼠大脑中单胺氧化酶和乙酰胆碱酯酶基因表达的氧化应激和下调。

Single or combined exposure to chlorpyrifos and cypermethrin provoke oxidative stress and downregulation in monoamine oxidase and acetylcholinesterase gene expression of the rat's brain.

机构信息

Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Dokki, Giza, 12618, Egypt.

Biochemistry Division, Faculty of Science, Cairo University, Giza, 12613, Egypt.

出版信息

Environ Sci Pollut Res Int. 2020 Apr;27(11):12692-12703. doi: 10.1007/s11356-020-07864-8. Epub 2020 Feb 1.

Abstract

The extensive uses of organophosphates and pyrethroids have made it necessary to investigate the neurotoxicity of their combination as they may implicate in the neurodegenerative syndromes. Monoamine oxidase-A (MAO-A) and acetylcholinesterase (AChE) gene expression in the rat brain were evaluated after independent and combined intoxications with chlorpyrifos and cypermethrin. Twenty-four mature male rats were equally distributed into four groups. The first one was kept as a control group, whereas the second, third and fourth were orally gavage with chlorpyrifos (16.324 mg/kg), cypermethrin (25.089 mg/kg) and their combination (9.254 mg/kg), respectively, for 4 weeks. As compared to the control group, intoxications with chlorpyrifos and/or cypermethrin revealed significant (P < 0.05) declines in the levels of brain neurotransmitters (dopamine and serotonin) plus the enzymatic activities of MAO-A, AChE and sodium-potassium adenosine triphosphatase. The mRNA genes expression of MAO-A and AChE have also confirmed the enzymatic actions. Moreover, the oxidative injury recorded as the levels of malondialdehyde and nitric oxide markedly increased (P < 0.01), while the total thiol content reduced and the histopathological outcomes have confirmed these impacts. In conclusion, chlorpyrifos and cypermethrin revealed antagonistic inhibitions on the brain MAO-A and AChE gene regulation through neurotransmission deteriorations and oxidative damage, which could describe their contributions in the neuropathological progressions.

摘要

有机磷酸酯和拟除虫菊酯的广泛应用使得研究它们的组合的神经毒性变得必要,因为它们可能与神经退行性综合征有关。在单独和联合染毒氯吡噁磷和氯菊酯后,评估了大鼠大脑中单胺氧化酶-A(MAO-A)和乙酰胆碱酯酶(AChE)基因的表达。24 只成熟雄性大鼠平均分为四组。第一组作为对照组,而第二、第三和第四组分别经口灌胃氯吡噁磷(16.324mg/kg)、氯菊酯(25.089mg/kg)和它们的混合物(9.254mg/kg),持续 4 周。与对照组相比,氯吡噁磷和/或氯菊酯染毒导致脑神经递质(多巴胺和 5-羟色胺)水平以及 MAO-A、AChE 和钠钾三磷酸腺苷酶的酶活性显著下降(P<0.05)。MAO-A 和 AChE 的 mRNA 基因表达也证实了酶的作用。此外,丙二醛和一氧化氮水平记录的氧化损伤明显增加(P<0.01),而总巯基含量降低,组织病理学结果证实了这些影响。总之,氯吡噁磷和氯菊酯通过神经传递恶化和氧化损伤对大脑 MAO-A 和 AChE 基因调控表现出拮抗抑制作用,这可以说明它们在神经病理学进展中的作用。

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