纳米氧化铈和铈/锌纳米复合材料的特性及其通过控制氧化应激和胰岛素抵抗在大鼠模型中防治肥胖的治疗作用。
Nano cerium oxide and cerium/zinc nanocomposites characterization and therapeutic role in combating obesity via controlling oxidative stress and insulin resistance in rat model.
机构信息
Inorganic Chemistry Department, National Research Centre, 33 El-Bohouth St., Dokki, P.O. 12622, Cairo, Egypt.
Pharmacology Department, National Research Centre, 33 El-Bohouth St., Dokki, P.O. 12622, Cairo, Egypt.
出版信息
J Trace Elem Med Biol. 2023 Dec;80:127312. doi: 10.1016/j.jtemb.2023.127312. Epub 2023 Sep 22.
BACKGROUND
CeONPs and ZnONPs can curb the increase of cholesterol and triglycerides observed in rats with non-alcoholic fatty liver disease. It was suggested that CeO NPs could potentially have an insulin-sensitizing effect, specifically on adipose tissue and skeletal muscle. It was reported that ZnONPs combat the increase of insulin resistance observed in obese rats and could be beneficial value in NAFLD. In our previous work, ZnO-NPs manifested valuable anti-obesity effects via lowering body weight gain, oxidative stress, BMI, lipids, and insulin resistance.
METHODS
In the present study, cerium oxide nanoparticles (A-1) and cerium/zinc nanocomposites (A-2 and A-3) were synthesized by solgel to investigate their role on oxidative stress, adipocyte hormones, and insulin resistance in an obese rat model. X-ray diffraction, HRTEM, SEM, and XPS were carried out to confirm the crystal structure, the particle size, the morphology of the nanoparticles and the oxidation states.
RESULTS
The Rietveld refinement has also been executed on A-1 (chi = 1.00; average Bragg = 2.92%; R-factor = 2.45%) and on A-2 (R = 9.87%, R= 9.68%, χ = 1.04, G = 1.02). The XPS spectra indicated the presence of Ce in + 4 and + 3 oxidation states and Zn as ZnO and ZnO.OH. Cerium oxide and ZnO crystal sizes lie in the range 40.53-45.01 and 40.53-45.01 nm, respectively. The results indicated that treating obese rats with any of the tested nano compounds (5 mg or 10 mg/Kg) lowered plasma cholesterol, triglycerides, LDL, insulin resistance, glucose, and BMI significantly relative to obese group values. On the other hand, HDL increased significantly in obese rats after treatment with either A-2 or A-3 compared to obese rats. The current investigation showed antioxidant activities for A-1, A-2, and A3 as evidenced by the significant increase in GSH level and a significant decrease in MDA.
CONCLUSION
It was found that A-1, A-2, and A-3 have an efficient therapeutic role in treating of obesity-related hyperlipidemia, oxidative stress and insulin resistance. The results of A-2 and A-3 were more pronounced than those of A-1. The use of Zn/Ce nanocomposite (that have positive characteristics) in combating obesity and its complications could be become a new trend in therapeutic application for a management of obesity.
背景
CeONPs 和 ZnONPs 可抑制非酒精性脂肪肝疾病大鼠胆固醇和甘油三酯的增加。有研究表明 CeO NPs 可能具有胰岛素增敏作用，特别是对脂肪组织和骨骼肌。有报道称，ZnONPs 可对抗肥胖大鼠的胰岛素抵抗增加，并可能对 NAFLD 具有有益价值。在我们之前的工作中，氧化锌纳米粒子（A-1）表现出有价值的抗肥胖作用，可降低体重增加、氧化应激、BMI、脂质和胰岛素抵抗。
方法
在本研究中，通过溶胶-凝胶法合成了氧化铈纳米粒子（A-1）和铈/锌纳米复合材料（A-2 和 A-3），以研究它们在肥胖大鼠模型中对氧化应激、脂肪细胞激素和胰岛素抵抗的作用。X 射线衍射、高分辨率透射电子显微镜、扫描电子显微镜和 X 射线光电子能谱用于确认晶体结构、颗粒尺寸、纳米粒子的形态和氧化态。
结果
A-1（chi = 1.00；平均布拉格 = 2.92%；R 因子 = 2.45%）和 A-2（R = 9.87%，R = 9.68%，chi = 1.04，G = 1.02）也进行了 Rietveld 精修。XPS 谱表明 Ce 存在于+4 和+3 氧化态，Zn 则存在于 ZnO 和 ZnO.OH。氧化铈和氧化锌的晶体尺寸分别在 40.53-45.01nm 和 40.53-45.01nm 范围内。结果表明，用测试的纳米化合物（5mg 或 10mg/kg）中的任何一种治疗肥胖大鼠，均可显著降低血浆胆固醇、甘油三酯、LDL、胰岛素抵抗、血糖和 BMI，与肥胖组相比有显著降低。另一方面，与肥胖大鼠相比，用 A-2 或 A-3 治疗后，肥胖大鼠的 HDL 显著增加。目前的研究表明，A-1、A-2 和 A3 具有抗氧化活性，这表现为 GSH 水平显著增加，MDA 显著降低。
结论
研究发现，A-1、A-2 和 A-3 对治疗肥胖相关的高脂血症、氧化应激和胰岛素抵抗具有有效的治疗作用。A-2 和 A-3 的效果比 A-1 更为显著。在对抗肥胖及其并发症方面，使用 Zn/Ce 纳米复合材料（具有积极特性）可能成为治疗肥胖的一种新趋势。
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