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褪黑素可预防敌敌畏诱导的大鼠神经行为改变。

Melatonin protects against diazinon-induced neurobehavioral changes in rats.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr University for Science and Technology (MUST), 6th of October City, Egypt,

出版信息

Neurochem Res. 2013 Oct;38(10):2227-36. doi: 10.1007/s11064-013-1134-9. Epub 2013 Aug 25.

Abstract

Diazinon is an organophosphorous pesticide with a prominent toxicity on many body organs. Multiple mechanisms contribute to diazinon-induced deleterious effects. Inhibition of acetyl-cholinesterase, cholinergic hyperstimulation, and formation of reactive oxygen species may play a role. On the other hand, melatonin is a pineal hormone with a well-known potent antioxidant activity and a remarkable modulatory effect on many behavioral processes. The present study revealed that oral diazinon administration (25 mg/kg) increased anxiety behavior in rats subjected to elevated plus maze and open-field tests possibly via the induction of changes in brain monoamines levels (dopamine, norepinephrine, and serotonin). Additionally, brain lipid peroxides measured as malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) levels were elevated, while the activity of brain glutathione peroxidase enzyme was reduced by diazinon. Co-administration of oral melatonin (10 mg/kg) significantly attenuated the anxiogenic activity of diazinon, rebalanced brain monoamines levels, decreased brain MDA and TNF-α levels, and increased the activity of brain glutathione peroxidase enzyme.

摘要

敌敌畏是一种有机磷农药,对许多身体器官都有明显的毒性。多种机制导致敌敌畏产生有害影响。乙酰胆碱酯酶抑制、胆碱能过度刺激和活性氧形成可能起作用。另一方面,褪黑素是一种松果腺激素,具有很强的抗氧化活性,对许多行为过程具有显著的调节作用。本研究表明,口服敌敌畏(25 毫克/公斤)给药可通过诱导大脑单胺水平(多巴胺、去甲肾上腺素和血清素)的变化,增加高架十字迷宫和旷场试验中大鼠的焦虑行为。此外,敌敌畏还会导致脑脂质过氧化物(以丙二醛 MDA 和肿瘤坏死因子-α TNF-α 表示)水平升高,而脑谷胱甘肽过氧化物酶的活性降低。口服褪黑素(10 毫克/公斤)的共同给药可显著减弱敌敌畏的致焦虑作用,使大脑单胺水平恢复平衡,降低大脑 MDA 和 TNF-α 水平,并增加大脑谷胱甘肽过氧化物酶的活性。

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