Aluminum and ABC transporter activity

IF 4.2 3区 环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2024-04-20 DOI:10.1016/j.etap.2024.104451
Goezde Oezen , Lisa Kraus , Eva-Maria Schentarra , Jan Stephan Bolten , Joerg Huwyler , Gert Fricker
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Abstract

Aluminum is the third most common element on Earth´s crust and despite its wide use in our workaday life it has been associated with several health risks after overexposure. In the present study the impact of aluminum salts upon ABC transporter activity was studied in the P-GP-expressing human blood-brain barrier cell line hCMEC/D3, in MDCKII cells overexpressing BCRP and MRP2, respectively, and in freshly isolated, functionally intact kidney tubules from Atlantic killifish (Fundulus heteroclitus), which express the analog ABC transporters, P-gp, Bcrp and Mrp2. In contrast to previous findings with heavy metals salts (cadmium(II) chloride or mercury(II) chloride), which have a strong inhibitory effect on ABC transporter activity, or zinc(II) chloride and sodium arsenite, which have a stimulatory effect upon ABC transport function, the results indicate no modulatory effect of aluminum salts on the efflux activity of the human ABC transporters P-GP, BCRP and MRP2 nor on the analog transporters P-gp, Bcrp and Mrp2.

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铝和 ABC 转运体的活性
铝是地壳中第三种最常见的元素,尽管它在我们的日常生活中被广泛使用,但过度接触后仍会对健康造成危害。本研究分别在表达 P-GP 的人血脑屏障细胞系 hCMEC/D3、过表达 BCRP 和 MRP2 的 MDCKII 细胞以及新鲜分离的、功能完整的大西洋鳉(Fundulus heteroclitus)肾小管中研究了铝盐对 ABC 转运体活性的影响。与以前用重金属盐(氯化镉(II)或氯化汞(II))(它们对 ABC 转运体的活性有很强的抑制作用)或氯化锌(II)和亚砷酸钠(它们对 ABC 转运功能有刺激作用)进行研究的结果不同,研究结果表明铝盐对人类 ABC 转运体 P-GP、BCRP 和 MRP2 的外流活性没有调节作用,对模拟转运体 P-gp、Bcrp 和 Mrp2 也没有调节作用。
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来源期刊
CiteScore
7.00
自引率
4.70%
发文量
185
审稿时长
34 days
期刊介绍: Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.
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