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氧化铜纳米颗粒对大鼠的神经病理学和认知效应及用石榴汁进行预防的试验。

Neuropathological and Cognitive Effects Induced by CuO-NPs in Rats and Trials for Prevention Using Pomegranate Juice.

机构信息

Faculty of Veterinary Medicine, Pathology Department, Cairo University, P.O. Box 12211, Giza, Egypt.

Faculty of Veterinary Medicine, Biochemistry Department, Cairo University, Giza, Egypt.

出版信息

Neurochem Res. 2021 May;46(5):1264-1279. doi: 10.1007/s11064-021-03264-7. Epub 2021 Feb 11.

DOI:10.1007/s11064-021-03264-7
PMID:33570729
Abstract

Copper oxide nanoparticles (CuO-NPs) are extensively utilized in several industries and in pharmaceutical production. This excess exposure elevates the concern about its expected poisonous impacts on humans and animals. Pomegranate juice (PJ) is a natural source of polyphenols and exhibits potent antioxidant activities. Our experiment intended to explore the neurobehavioral and toxicopathological impacts of CuO-NPs and to explain the mechanistic role of PJ to reduce their toxicity. Thirty Wistar albino rats received the subsequent materials through oral gavage, every day for 28d: (1) normal saline, (2) 3 mL/kg bwt PJ, (3) 6 mL/kg bwt PJ, (4) 300 mg/kg bwt CuO-NPs, (5) CuO-NPs + 3 mL/kg bwt PJ, (6) CuO-NPs + 6 mL/kg bwt PJ. Continuous exposure to CuO-NPs caused a significant elevation of MDA levels and reduction of total antioxidant capacity associated with remarkable pathological alterations in all brain regions including cerebrum, hippocampus and cerebellum. Progressive decline of memory along with cognitive and psychiatric disturbances were observed in rats exposed to CuO-NPs not in PJ co-treated rats. Continuous exposure to CuO-NPs caused over expression of the immunohistochemical markers of caspase-3, iNOS and GFAP altogether with DAN fragmentation and down-regulation of HO-1 and Nrf2 gene in the whole brain tissues. Conversely, rats co-treated with PJ showed dose dependent improvements in the entire toxicological, behavioral, and pathological parameters. We showed that PJ had the ability to reduce the oxidative stress damage via up-regulation of HO-1 and Nrf2 genes in the brain. So that PJ had the ability to protect the brain and DNA from further damage.

摘要

氧化铜纳米粒子(CuO-NPs)广泛应用于多个行业和制药生产中。这种过度暴露引起了人们对其对人类和动物预期毒性影响的关注。石榴汁(PJ)是多酚的天然来源,具有很强的抗氧化活性。我们的实验旨在探讨 CuO-NPs 的神经行为和毒理学影响,并解释 PJ 减少其毒性的机制作用。30 只 Wistar 白化大鼠通过口服灌胃接受以下材料,每天一次,共 28d:(1)生理盐水,(2)3 mL/kg bwt PJ,(3)6 mL/kg bwt PJ,(4)300 mg/kg bwt CuO-NPs,(5)CuO-NPs+3 mL/kg bwt PJ,(6)CuO-NPs+6 mL/kg bwt PJ。连续暴露于 CuO-NPs 会导致 MDA 水平显著升高和总抗氧化能力降低,所有大脑区域(包括大脑、海马体和小脑)都出现明显的病理改变。与单独暴露于 CuO-NPs 的大鼠相比,同时接受 PJ 治疗的大鼠记忆能力逐渐下降,认知和精神障碍。连续暴露于 CuO-NPs 会导致整个大脑组织中 caspase-3、iNOS 和 GFAP 的免疫组织化学标志物过度表达,以及 DAN 片段化和 HO-1 和 Nrf2 基因下调。相反,同时接受 PJ 治疗的大鼠在所有毒理学、行为和病理参数方面均显示出剂量依赖性改善。我们表明,PJ 通过上调大脑中的 HO-1 和 Nrf2 基因,具有减轻氧化应激损伤的能力。因此,PJ 具有保护大脑和 DNA 免受进一步损伤的能力。

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