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The ameliorative effect of nanoselenium on histopathological and biochemical alterations induced by melamine toxicity on the brain of adult male albino rats
NeuroToxicology ( IF 3.4 ) Pub Date : 2021-07-01 , DOI: 10.1016/j.neuro.2021.06.006
Dina W Bashir 1 , Maha M Rashad 2 , Yasmine H Ahmed 1 , Elsayed A Drweesh 3 , Eman A M Elzahany 3 , Khaled S Abou-El-Sherbini 3 , Ebtihal M M El-Leithy 1
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Melamine is a chemical substance used as a food adulterant because of its high nitrogen content; it is known to induce neurotoxicity, thereby adversely affecting the central nervous system. The biocompatibility, bioavailability, lower toxicity, and the large surface area of nanosized selenium relative to its other forms indicate that selenium nanoparticles (SeNPs) have a potential ameliorative effect against melamine-induced neurotoxicity. In this study, we tested this hypothesis using 40 adult male albino rats that were randomly assigned into four groups (n = 10 per group): group I rats served as the untreated negative controls and were fed with standard diet and distilled water; group II rats were orally treated with melamine (300 mg/kg body weight/d); group III rats orally received melamine (300 mg/kg body weight/d) and SeNPs (2 mg/kg body weight/d); and group IV rats received SeNPs only (2 mg/kg body weight/d) for 28 days. Blood and brain samples were collected from all rats and processed for biochemical, histopathological, and immunohistochemical investigations. SeNPs were encapsulated in starch as a natural stabilizer and a size-controlling agent (SeNP@starch). The prepared SeNPs were characterized using different techniques. Inductively coupled plasma-optical emission spectrometry (ICP-OES) indicated that the percentage of selenium loaded in starch was 1.888 %. Powder x-ray diffractometer (XRD) was used to investigate the crystalline structure of the Se-NP@starch, to be tubular and composed of amorphous starch as well as metallic selenium. Thermogravimetric analysis confirmed the thermal stability of the product and determined the interactions among the different components. Transmission electron microscope demonstrated the spherical shape of SeNPs and their dispersion into starch surface as well as evaluating their size in nanoscale (range 20−140 nm). Our results revealed that the melamine- exposed rats had significantly elevated in malondialdehyde levels, significantly reduced in total antioxidant capacity, down-regulated expression of the antioxidant related genes Nrf2 (nuclear factor erythroid 2–related factor 2) and GPx (glutathione peroxidase), as well as up-regulated expression of the apoptosis-related gene Bax (B-cell lymphoma 2–associated X protein), with down regulation of Bcl-2 (B-cell lymphoma 2). Histopathological examination exhibited several alterations in the cerebrum, cerebellum, and hippocampus of the treated rats compared with the controls. Neuronal degeneration, vacuolation of the neuropils, and pericellular and perivascular spaces were observed. In addition, the pyramidal and granular cell layers of the hippocampus and cerebellum, respectively, were found to have significantly reduced thickness. Furthermore, a significant decrease in the percentage area of the glial fibrillary acidic protein and a significant increase in the percentage area of caspase-3 were noted. On the other hand, co-treatment with SeNPs partially ameliorated these alterations. A significant reduction in malondialdehyde levels; a non- significant elevation in total antioxidant capacity; up-regulation, upregulation of Nrf2, GPx, and Bcl-2 and downregulation of Bax were recorded. Neuronal degeneration, vacuolation of neuropils, and pericellular spaces were reduced. The pyramidal and granular cell layers restored their normal thickness. The percentage area of the glial fibrillary acidic protein significantly increased, whereas that of caspase-3 significantly decreased. In conclusion, SeNPs have an ameliorative effect against melamine-induced neurotoxicity in albino rats.



中文翻译:

纳米硒对三聚氰胺毒性对成年雄性白化大鼠脑组织病理学和生化改变的改善作用

三聚氰胺是一种化学物质,因其含氮量高而被用作食品掺假剂;已知它会引起神经毒性,从而对中枢神经系统产生不利影响。纳米硒相对于其他形式的生物相容性、生物利用度、较低的毒性和较大的表面积表明硒纳米颗粒 (SeNPs) 对三聚氰胺诱导的神经毒性具有潜在的改善作用。在这项研究中,我们使用 40 只成年雄性白化病大鼠来检验这一假设,这些大鼠被随机分为四组(每组 n = 10):第一组大鼠作为未治疗的阴性对照,喂食标准饮食和蒸馏水;II组大鼠口服三聚氰胺(300mg/kg体重/d);III组大鼠口服三聚氰胺(300 mg/kg体重/d)和SeNPs(2 mg/kg体重/d);IV组大鼠仅接受SeNPs(2 mg/kg体重/天)28天。从所有大鼠收集血液和脑样本,并进行生化、组织病理学和免疫组织化学研究。SeNPs 被包裹在淀粉中作为天然稳定剂和尺寸控制剂 (SeNP@starch)。使用不同的技术对制备的 SeNPs 进行了表征。电感耦合等离子体发射光谱法 (ICP-OES) 表明,淀粉中硒负载的百分比为 1.888 %。粉末 X 射线衍射仪 (XRD) 用于研究 Se-NP@starch 的晶体结构,它是管状的,由无定形淀粉和金属硒组成。热重分析证实了产品的热稳定性并确定了不同组分之间的相互作用。透射电子显微镜显示了 SeNPs 的球形形状及其在淀粉表面的分散性,并评估了它们的纳米级尺寸(范围 20-140 nm)。我们的研究结果表明,三聚氰胺暴露的大鼠丙二醛水平显着升高,总抗氧化能力显着降低,抗氧化相关基因的表达下调Nrf2(核因子红细胞 2 相关因子 2)和GPx(谷胱甘肽过氧化物酶),以及凋亡相关基因Bax(B 细胞淋巴瘤 2 相关 X 蛋白)的表达上调,Bcl- 2(B细胞淋巴瘤2)。组织病理学检查显示,与对照组相比,治疗组大鼠的大脑、小脑和海马发生了一些变化。观察到神经元变性、神经纤维的空泡形成以及细胞周围和血管周围的空间。此外,海马和小脑的锥体细胞层和颗粒细胞层的厚度分别显着降低。此外,注意到胶质纤维酸性蛋白的百分比面积显着降低,caspase-3 的百分比面积显着增加。另一方面,与SeNPs的共同处理部分地改善了这些改变。丙二醛水平显着降低;总抗氧化能力不显着升高;上调,上调记录了Nrf2、GPx 和 Bcl-2以及Bax的下调。神经元变性、神经纤维的空泡化和细胞周围空间减少。锥体和颗粒细胞层恢复正常厚度。胶质纤维酸性蛋白的百分比面积显着增加,而 caspase-3 的百分比面积显着降低。总之,SeNPs 对白化大鼠三聚氰胺诱导的神经毒性具有改善作用。

更新日期:2021-07-07
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