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亚慢性氯化镉暴露的神经和肾毒性及硒纳米粒子的潜在化学保护作用。

Neuro- and nephrotoxicity of subchronic cadmium chloride exposure and the potential chemoprotective effects of selenium nanoparticles.

机构信息

Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.

Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.

出版信息

Metab Brain Dis. 2017 Oct;32(5):1659-1673. doi: 10.1007/s11011-017-0053-x. Epub 2017 Jun 28.

Abstract

Cadmium (Cd) exposure leads to production of reactive oxygen species (ROS), which are associated with Cd-induced neurotoxicity and nephrotoxicity. Selenium nanoparticles (Se-NPs) have high bioavailability and antioxidant activities so it attracted wide spread attention. The present study examined the possible ameliorative effect of Se-NPs with diameters of 3-5 nm and 10-20 nm against cadmium chloride (CdCl)-induced neuro- and nephrotoxicity in rats. Rats were treated with Se-NPs (0 or 0.5 mg/kg BW, s.c.) one hour prior to the CdCl (0 or 5 mg/kg BW, p.o.). Pretreatment with Se-NPs significantly decreased CdCl-induced elevation of serum kidney and brain damage biomarkers; lipid peroxidation; the percent of DNA fragmentation and nearly normalized the activity of acetylcholinesterase (AchE) and significantly increased the activity and expression of antioxidant biomarkers in the RNA and protein levels. Se-NPs also attenuated CdCl-induced upregulation of kidney and brain pro-apoptotic B-cell CLL/lymphoma 2 associated X (Bax) RNA and protein levels with preventing the increased body burden of Cd and the altered Fe and Cu homeostasis. Histopathological analysis confirmed the biochemical and molecular outcomes. Our data stated that Se-NPs appear to be effective in ameliorating the adverse neurological and nephrotoxic effects induced by CdCl partially through the scavenging of free radicals, metal ion chelation, averting apoptosis and altering the cell-protective pathways. The results indicated that Se-NPs could potentially included as an additive to Cd-based industries to control Cd-induced brain and renal injury.

摘要

镉(Cd)暴露会导致活性氧(ROS)的产生,这与 Cd 诱导的神经毒性和肾毒性有关。纳米硒(Se-NPs)具有高生物利用度和抗氧化活性,因此引起了广泛关注。本研究探讨了直径为 3-5nm 和 10-20nm 的 Se-NPs 对氯化镉(CdCl)诱导的大鼠神经和肾毒性的可能改善作用。大鼠在给予 CdCl(0 或 5mg/kg BW,po)前 1 小时给予 Se-NPs(0 或 0.5mg/kg BW,sc)。预处理 Se-NPs 可显著降低 CdCl 诱导的血清肾和脑损伤生物标志物升高;脂质过氧化;DNA 片段化的百分比,并使乙酰胆碱酯酶(AchE)的活性几乎正常化,并在 RNA 和蛋白质水平上显著增加抗氧化生物标志物的活性和表达。Se-NPs 还可减弱 CdCl 诱导的肾脏和大脑促凋亡 B 细胞 CLL/淋巴瘤 2 相关 X(Bax)RNA 和蛋白水平的上调,防止 Cd 体内负荷增加和铁、铜稳态改变。组织病理学分析证实了生化和分子结果。我们的数据表明,Se-NPs 似乎可以通过清除自由基、金属离子螯合、避免细胞凋亡和改变细胞保护途径,有效改善 CdCl 诱导的不良神经和肾毒性作用。结果表明,Se-NPs 可能可作为 Cd 基工业的添加剂,以控制 Cd 诱导的脑和肾损伤。

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