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二苯甲酮-3可穿过血脑屏障,提高细胞外谷氨酸水平,并诱导大鼠海马体和额叶皮质中的凋亡过程。

Benzophenone-3 Passes Through the Blood-Brain Barrier, Increases the Level of Extracellular Glutamate, and Induces Apoptotic Processes in the Hippocampus and Frontal Cortex of Rats.

作者信息

Pomierny Bartosz, Krzyżanowska Weronika, Broniowska Żaneta, Strach Beata, Bystrowska Beata, Starek-Świechowicz Beata, Maciejska Alicja, Skórkowska Alicja, Wesołowska Julita, Walczak Maria, Budziszewska Bogusława

机构信息

Department of Biochemical Toxicology.

Department of Toxicology, Chair of Toxicology, Medical College, Jagiellonian University, 30-688 Kraków, Poland.

出版信息

Toxicol Sci. 2019 Oct 1;171(2):485-500. doi: 10.1093/toxsci/kfz160.

Abstract

Benzophenone-3 is the most commonly used UV filter. It is well absorbed through the skin and gastrointestinal tract. Its best-known side effect is the impact on the function of sex hormones. Little is known about the influence of BP-3 on the brain. The aim of this study was to show whether BP-3 crosses the blood-brain barrier (BBB), to determine whether it induces nerve cell damage in susceptible brain structures, and to identify the mechanism of its action in the central nervous system. BP-3 was administered dermally during the prenatal period and adulthood to rats. BP-3 effect on short-term and spatial memory was determined by novel object and novel location recognition tests. BP-3 concentrations were assayed in the brain and peripheral tissues. In brain structures, selected markers of brain damage were measured. The study showed that BP-3 is absorbed through the rat skin, passes through the BBB. BP-3 raised oxidative stress and induced apoptosis in the brain. BP-3 increased the concentration of extracellular glutamate in examined brain structures and changed the expression of glutamate transporters. BP-3 had no effect on short-term memory but impaired spatial memory. The present study showed that dermal BP-3 exposure may cause damage to neurons what might be associated with the increase in the level of extracellular glutamate, most likely evoked by changes in the expression of GLT-1 and xCT glutamate transporters. Thus, exposure to BP-3 may be one of the causes that increase the risk of developing neurodegenerative diseases.

摘要

二苯甲酮 - 3是最常用的紫外线过滤剂。它可通过皮肤和胃肠道被充分吸收。其最广为人知的副作用是对性激素功能的影响。关于二苯甲酮 - 3对大脑的影响知之甚少。本研究的目的是表明二苯甲酮 - 3是否能穿过血脑屏障(BBB),确定它是否会在易感脑结构中诱导神经细胞损伤,并确定其在中枢神经系统中的作用机制。在孕期和成年期给大鼠经皮施用二苯甲酮 - 3。通过新物体和新位置识别测试来确定二苯甲酮 - 3对短期和空间记忆的影响。测定大脑和外周组织中二苯甲酮 - 3的浓度。在脑结构中,测量选定的脑损伤标志物。研究表明,二苯甲酮 - 3可通过大鼠皮肤吸收,穿过血脑屏障。二苯甲酮 - 3会增加大脑中的氧化应激并诱导细胞凋亡。二苯甲酮 - 3会增加所检测脑结构中细胞外谷氨酸的浓度,并改变谷氨酸转运体的表达。二苯甲酮 - 3对短期记忆没有影响,但会损害空间记忆。本研究表明,经皮接触二苯甲酮 - 3可能会导致神经元损伤,这可能与细胞外谷氨酸水平的升高有关,很可能是由GLT - 1和xCT谷氨酸转运体表达的变化引起的。因此,接触二苯甲酮 - 3可能是增加神经退行性疾病发病风险的原因之一。

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