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利用银鲶(Rhamdia quelen)作为实验模型研究噻虫嗪诱导的神经毒性的嘌呤能信号转导作为潜在靶点。

Purinergic signaling as potential target of thiamethoxam-induced neurotoxicity using silver catfish (Rhamdia quelen) as experimental model.

机构信息

Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.

Department of Physiology and Pharmacology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.

出版信息

Mol Cell Biochem. 2018 Dec;449(1-2):39-45. doi: 10.1007/s11010-018-3340-x. Epub 2018 Feb 26.

Abstract

Thiamethoxam is a broad-spectrum pesticide widely used in agricultural practice throughout the world. Worryingly, this pesticide is considered a potential contaminant on the surface and underground water, being a significant risk to aquatic ecosystems and humans. In this sense, we decided to evaluate the activity of enzymes belonging to purinergic system, which is linked with regulation of extracellular nucleotides and nucleosides, as adenosine triphosphate (ATP) and adenosine (Ado) molecules involved in the regulation of immune and inflammatory responses. Such as the neurotoxic effects of thiamethoxam remain poorly understood, the aim of this study was to evaluate whether purinergic signaling may be considered a potential target of thiamethoxam-induced neurotoxicity in silver catfish (Rhamdia quelen). Brain ectonucleoside triphosphate diphosphohydrolase (ATP as substrate) and 5'-nucleotidases activities were inhibited at 3.75 µg L after 24 h of exposure and at 1.125 and 3.75 µg L after 96 h of exposure compared with the control group. On the other hand, brain adenosine deaminase activity was stimulated at 3.75 µg L after 24 h of exposure and at 1.125 and 3.75 µg L after 96 h of exposure compared with the control group. Brain ATP levels increased at 3.75 µg L after 24 h of exposure and at 1.125 and 3.75 µg L after 96 h of exposure compared with the control group, while the Ado levels decreased. The enzymatic activity of the purinergic signaling did not return to control levels after a 48-h recovery period, revealing the potential neurotoxic effects of thiamethoxam. In summary, the brain purinergic signaling may be considered a potential target for thiamethoxam-induced neurotoxicity in silver catfish.

摘要

噻虫嗪是一种在世界范围内农业实践中广泛使用的广谱杀虫剂。令人担忧的是,这种杀虫剂被认为是地表水和地下水的潜在污染物,对水生生态系统和人类构成重大风险。在这种情况下,我们决定评估属于嘌呤能系统的酶的活性,该系统与细胞外核苷酸和核苷的调节有关,如三磷酸腺苷(ATP)和腺苷(Ado)分子,它们参与免疫和炎症反应的调节。由于噻虫嗪的神经毒性作用仍知之甚少,本研究旨在评估嘌呤能信号是否可被视为银鲶(Rhamdia quelen)中噻虫嗪诱导的神经毒性的潜在靶标。暴露 24 小时后,在 3.75 µg/L 时脑外核苷酸三磷酸二磷酸水解酶(以 ATP 为底物)和 5'-核苷酸酶活性被抑制,暴露 96 小时后在 1.125 和 3.75 µg/L 时被抑制,与对照组相比。另一方面,暴露 24 小时后,在 3.75 µg/L 时脑腺苷脱氨酶活性被刺激,暴露 96 小时后在 1.125 和 3.75 µg/L 时被刺激,与对照组相比。暴露 24 小时后,在 3.75 µg/L 时脑 ATP 水平升高,暴露 96 小时后在 1.125 和 3.75 µg/L 时升高,与对照组相比,而 Ado 水平降低。暴露 48 小时恢复后,嘌呤能信号的酶活性未恢复到对照水平,表明噻虫嗪具有潜在的神经毒性作用。总之,脑嘌呤能信号可能被视为银鲶中噻虫嗪诱导的神经毒性的潜在靶标。

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