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通过口服藏红花提取物预防锌纳米颗粒引起的神经毒性和认知障碍。

Prevention of neurotoxicity and cognitive impairment induced by zinc nanoparticles by oral administration of saffron extract.

机构信息

Laboratory of Integrative Physiology, Department of Sciences of Life, Faculty of Sciences of Bizerte, University of Carthage, Jarzouna, Tunisia.

Department of Mathematical and Fluid Physics, Environmental Toxicology and Biology Group, UNED, Madrid, Spain.

出版信息

J Anim Physiol Anim Nutr (Berl). 2023 Nov;107(6):1473-1494. doi: 10.1111/jpn.13848. Epub 2023 May 29.

DOI:10.1111/jpn.13848
PMID:37246965
Abstract

The accumulation of relatively higher dose of zinc oxide nanoparticles in brain was reported to produce neurotoxicity. Indeed, nanoparticles have a high ability to penetrate biological membranes and be uptaken by cells, which may cause cell disorders and physiological dysfunctions. The aim of the current study was to evaluate, whether oral administration of saffron extract, in rats, can protect from neurotoxicity and behavioural disturbances induced by chronic administration of ZnO-NPs. Daily oral administration of ZnO-NPs was performed for 21 consecutive days to induce oxidative stress-like situation. Then after the saffron extract was concomitantly administrated in several rat groups to overcome the nanotoxicological effect induced by ZnO-NPs. In the frontal cortex, the hippocampus and the cerebellum, ZnO-NPs induced a H O -oxydative stress-like effect reflected in reduced enzymatic activities of catalase, superoxide dismutase and glutathione S-transferase, and decreased acetylcholinesterase activity. In addition, increased levels of proinflammatory interleukins IL-6 and IL-1-⍺ occurred in the hippocampus, reveal the existence of brain inflammation. The concomitant administration of saffron extract to animals exposed to ZnO-NPs prevented the enhanced anxiety-related to the behaviour in the elevated plus-maze test, the open field test and preserved spatial learning abilities in the Morris water maze. Moreover, animals exposed to ZnO-NPs and saffron showed abnormal activity of several antioxidant enzymes as well as acetylcholinesterase activity, an effect that may underly the preserved anxiety-like behaviour and spatial learning abilities observed in these animals. Saffron extract has a potential beneficial therapeutic effect: antioxidant, anti-inflammatory and neuroprotective agent.

摘要

据报道,相对较高剂量的氧化锌纳米颗粒在大脑中的积累会产生神经毒性。事实上,纳米颗粒具有很高的穿透生物膜和被细胞摄取的能力,这可能导致细胞紊乱和生理功能障碍。本研究的目的是评估藏红花提取物是否能通过口服给药来保护大鼠免受慢性给予 ZnO-NPs 引起的神经毒性和行为障碍。连续 21 天每天口服给予 ZnO-NPs,以诱导氧化应激样情况。然后,在几个大鼠组中同时给予藏红花提取物,以克服 ZnO-NPs 引起的纳米毒性作用。在大脑皮质、海马体和小脑,ZnO-NPs 诱导产生 H2O2 氧化应激样效应,表现为过氧化氢酶、超氧化物歧化酶和谷胱甘肽 S-转移酶的酶活性降低,乙酰胆碱酯酶活性降低。此外,海马体中促炎细胞因子白细胞介素-6 和白细胞介素-1-α的水平升高,表明存在脑炎症。将藏红花提取物同时给予暴露于 ZnO-NPs 的动物,可防止在高架十字迷宫测试、旷场测试中增强的焦虑相关行为,并可保留在水迷宫中的空间学习能力。此外,暴露于 ZnO-NPs 和藏红花的动物表现出几种抗氧化酶和乙酰胆碱酯酶活性的异常,这种作用可能是这些动物中观察到的焦虑样行为和空间学习能力得到保留的基础。藏红花提取物具有潜在的有益治疗作用:抗氧化剂、抗炎剂和神经保护剂。

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