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铅(Pb)暴露会引起 5-羟色胺能和加压素系统的生理改变,导致沙鼠出现焦虑样行为:BDMC 作为铅神经毒性和肾脏损伤的神经保护化合物的评估。

Lead (Pb) exposure induces physiological alterations in the serotoninergic and vasopressin systems causing anxiogenic-like behavior in Meriones shawi: Assessment of BDMC as a neuroprotective compound for Pb-neurotoxicity and kidney damages.

机构信息

Neurosciences, Pharmacology and Environment Team, Laboratory of Clinical, Experimental and Environmental Neurosciences, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco; Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh, Morocco.

Neurosciences, Pharmacology and Environment Team, Laboratory of Clinical, Experimental and Environmental Neurosciences, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco; Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh, Morocco; Cadi Ayyad University, Multidisciplinary Faculty of Safi, Department of Biology, Morocco.

出版信息

J Trace Elem Med Biol. 2021 May;65:126722. doi: 10.1016/j.jtemb.2021.126722. Epub 2021 Jan 23.

DOI:10.1016/j.jtemb.2021.126722
PMID:33524682
Abstract

BACKGROUND

Studies have shown that lead (Pb) is one of hazardous heavy metals with various adverse effects on human health including mental health; Pb can induce psychiatric disorders like anxiety. In the present work, we examined the potential of bisdemethoxycurcumin (BDMC) as a neuroprotective agent against lead induced anxiety inMeriones shawi (M. shawi).

METHODS

We asses, the potential of three consecutive day exposure to Pb (25 mg/kg body weight) in inducing anxiogenic effect, serotoninergic and vasopressinergic disruptions inM. shawi. This was done using neurobehavioral tests (open field, elevated plus maze), immunohistochemestry by anti-serotonin (5-HT), and anti-vasopressin (AVP) antibodies. We also measured the possible restorative potential of BDMC (30 mg/kg body weight), delivered by oral gavage. After that, a biochemical and histopathological studies were done.

RESULTS

Our results showed that lead exposure for three consecutive days increases significantly the 5-HT-immunoreactivity in dorsal raphe nucleus (DRN) accompanied with a significant enhancement of AVP-immunoreactivity in the cell bodies and fibers in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. In the collecting tube, AVP binds to the V2 receptor of the epithelial cells and increases the water permeability. Our results showed clearly the epithelial cells degeneration after lead exposure, then we suggest that the increased AVP could be a response to the hydric balance disrupted after degenerative effect of lead exposure on epithelial cells. BDMC produced an anxiolytic effect in meriones. Moreover, it restored 5-HT and AVP immunoreactivity within studying nuclei. The biochemical and histopathological studies showed that Pb induced renal damages. In addition, BDMC restored the renal alterations.

CONCLUSION

According to the obtained results, we suggest new pharmacological effects of BDMC; while it has an anxiolytic effect against Pb-induced anxiety by working on serotoninergic and vasopressinergic systems with an obvious restoration of the renal injuries induced by lead exposure.

摘要

背景

研究表明,铅(Pb)是一种危害极大的重金属,对人类健康有多种不良影响,包括心理健康;铅可引起焦虑等精神疾病。在本工作中,我们研究了双去甲氧基姜黄素(BDMC)作为一种神经保护剂,对抗 Meriones shawi(M. shawi)中铅诱导的焦虑的潜力。

方法

我们评估了连续三天暴露于 Pb(25mg/kg 体重)对 M. shawi 引起焦虑作用、5-羟色胺能和加压素能紊乱的潜在作用。这是通过神经行为测试(旷场实验、高架十字迷宫)、抗 5-羟色胺(5-HT)和抗加压素(AVP)抗体的免疫组织化学来完成的。我们还测量了 BDMC(30mg/kg 体重)通过口服灌胃的可能恢复潜力。之后进行了生化和组织病理学研究。

结果

我们的结果表明,连续三天暴露于铅可显著增加背侧中缝核(DRN)中的 5-HT 免疫反应性,同时显著增强下丘脑视上核(SON)和室旁核(PVN)细胞体和纤维中的 AVP 免疫反应性。在收集管中,AVP 与上皮细胞的 V2 受体结合,增加水的通透性。我们的结果清楚地显示了铅暴露后上皮细胞的退化,然后我们认为,AVP 的增加可能是对铅暴露对上皮细胞的退行性作用破坏水平衡的一种反应。BDMC 在 Meriones 中产生抗焦虑作用。此外,它恢复了研究核内的 5-HT 和 AVP 免疫反应性。生化和组织病理学研究表明,Pb 诱导了肾脏损伤。此外,BDMC 恢复了肾脏的改变。

结论

根据获得的结果,我们提出了 BDMC 的新的药理学作用;它通过作用于 5-羟色胺能和加压素能系统,对 Pb 诱导的焦虑具有抗焦虑作用,同时明显恢复了铅暴露引起的肾脏损伤。

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