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硫酸黏菌素和去铁酮对铅诱导的小鼠脑内变化的影响。

Effects of Salinomycin and Deferiprone on Lead-Induced Changes in the Mouse Brain.

机构信息

Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., Bl. 25, 1113 Sofia, Bulgaria.

Chemistry Department, Research and Development, BIOVET JSC, 39 Peter Rakov Street, 4550 Peshtera, Bulgaria.

出版信息

Int J Mol Sci. 2023 Feb 2;24(3):2871. doi: 10.3390/ijms24032871.

Abstract

Lead (Pb) is a highly toxic heavy metal that has deleterious effects on the central nervous system. This study aimed to investigate the effects of salinomycin (Sal) and deferiprone (DFP) on brain morphology and on the content of some essential elements in Pb-exposed mice. Adult male Institute of Cancer Research (ICR) mice were exposed to a daily dose of 80 mg/kg body weight ( b.w.) Pb(II) nitrate for 14 days and subsequently treated with Sal (16 mg/kg b.w.) or DFP (19 mg/kg b.w.) for another 14 days. At the end of the experimental protocol, the brains were processed for histological and inductively coupled plasma mass spectrometry (ICP-MS) analyses. Pb exposure resulted in a 50-fold increase in Pb concentration, compared with controls. Magnesium (Mg) and phosphorus (P) were also significantly increased by 22.22% and 17.92%, respectively. The histological analysis of Pb-exposed mice revealed brain pathological changes with features of neuronal necrosis. Brain Pb level remained significantly elevated in Sal- and DFP-administered groups (37-fold and 50-fold, respectively), compared with untreated controls. Treatment with Sal significantly reduced Mg and P concentrations by 22.56% and 18.38%, respectively, compared with the Pb-exposed group. Administration of Sal and DFP ameliorated brain injury in Pb-exposed mice and improved histological features. The results suggest the potential application of Sal and DFP for treatment of Pb-induced neurotoxicity.

摘要

铅(Pb)是一种剧毒重金属,对中枢神经系统有有害影响。本研究旨在探讨盐霉素(Sal)和去铁酮(DFP)对暴露于铅的小鼠大脑形态和某些必需元素含量的影响。成年雄性 Institute of Cancer Research(ICR)小鼠每天接受 80mg/kg 体重(b.w.)硝酸铅处理 14 天,随后再用 Sal(16mg/kg b.w.)或 DFP(19mg/kg b.w.)处理 14 天。在实验方案结束时,对大脑进行组织学和电感耦合等离子体质谱(ICP-MS)分析。与对照组相比,铅暴露导致铅浓度增加了 50 倍。镁(Mg)和磷(P)也分别增加了 22.22%和 17.92%。铅暴露小鼠的组织学分析显示出具有神经元坏死特征的大脑病理变化。与未处理的对照组相比,Sal 和 DFP 给药组的大脑铅水平仍显著升高(分别升高 37 倍和 50 倍)。与铅暴露组相比,Sal 处理显著降低了 Mg 和 P 浓度,分别降低了 22.56%和 18.38%。Sal 和 DFP 的给药改善了铅暴露小鼠的脑损伤并改善了组织学特征。结果表明,Sal 和 DFP 可能具有治疗铅诱导的神经毒性的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eed9/9918121/19b260fac05d/ijms-24-02871-g001.jpg

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