The therapeutic prospect of zinc oxide nanoparticles in experimentally induced diabetic nephropathy.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Samia A Abd El-Baset, Nehad F Mazen, Rehab S Abdul-Maksoud, Asmaa A A Kattaia
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引用次数: 3

Abstract

Diabetic nephropathy (DN) is the most frequent cause of end-stage renal failure. Zinc oxide nanoparticles (ZnO-NPs) are promising antidiabetic agents. Our aim was to evaluate the prospective efficacy of ZnO-NPs in treating DN in streptozotocin-induced diabetic rats. Rats were randomly dispersed into three sets: control group, DN group and DN + ZnO-NPs group. ZnO-NPs were given at a dose of 10 mg/kg/day by oral gavage for 4 weeks. Urine and blood samples were processed for biochemical analyses. Kidney samples were managed for light and electron microscopy studies. Immune histochemical staining of P53, aquaporin11 (AQP11) and mechanistic target of rapamycin (mTOR) were performed. Gene analyses of nephrin, podocin, beclin-1, LC3 and p62 were done. Administration of ZnO-NPs ameliorated the functional and histopathological alterations of the kidney in a rat model of diabetic nephropathy. ZnO-NPs retained the constancy of the glomerular filtration barrier and restored almost normal renal structure. This was confirmed by upregulation of mRNA expression of podocyte markers (nephrin and podocin) and AQP11 immune histochemical expression in the renal tubules. The beneficial outcomes of ZnO-NPs might be attributed to activation of autophagy through inhibiting mTOR signaling pathway. ZnO-NPs enhanced beclin-1 and LC3 mRNA expressions and reduced p62 mRNA expression. ZnO-NPs also exerted anti-apoptotic potential (evidenced by the decrease in p53 immune expression), anti-inflammatory and anti-oxidant effect [endorsed by suppression of serum cyclooxygenase-2 (COX-2) enzyme activity, tissue nuclear factor kappa beta (NF-κB) level and blood hypoxia-inducible factors (HIF-1α) level]. These results may point the way to an effective therapy of DN.Abbreviations: AQP11 Aquaporin11; BUN: Blood urea nitrogen; COX-2: Cyclooxygenase-2; DAB: 3, 3'-diaminobenzidine; DM: Diabetes mellitus; DN: Diabetic nephropathy; ELISA: Enzyme-linked immunosorbent assay; H&E: Hematoxylin & eosin; HIF-1α: Hypoxia-inducible factors; iNOS: inducible nitric oxide synthase; LC3: Microtubule-associated protein 1 light chain 3; mTOR: Mechanistic target of rapamycin; NF-κB: Nuclear factor kappa beta; NPs: Nanoparticles; PAS: Periodic acid Schiff; PCR: Polymerase chain reaction; PGE2: Prostaglandin E2; ROS: Reactive oxygen species; STZ: Streptozotocin; X ± SEM: Mean ± standard error of means; Zn: Zinc; ZnO-NPs: Zinc oxide nanoparticles.

氧化锌纳米颗粒治疗实验性糖尿病肾病的前景。
糖尿病肾病(DN)是终末期肾功能衰竭最常见的原因。氧化锌纳米颗粒(ZnO-NPs)是一种很有前途的抗糖尿病药物。我们的目的是评估ZnO-NPs治疗链脲佐菌素诱导的糖尿病大鼠DN的前瞻性疗效。将大鼠随机分为3组:对照组、DN组和DN + ZnO-NPs组。ZnO-NPs以10 mg/kg/天的剂量灌胃,连续4周。尿液和血液样本进行生化分析。对肾脏样本进行光镜和电子显微镜研究。对P53、水通道蛋白11 (AQP11)和雷帕霉素(mTOR)进行免疫组化染色。对nephrin、podocin、beclin-1、LC3、p62进行基因分析。给药ZnO-NPs可以改善糖尿病肾病大鼠模型肾脏的功能和组织病理学改变。ZnO-NPs保留了肾小球滤过屏障的稳定性,恢复了几乎正常的肾脏结构。肾小管足细胞标记物(nephrin和podocin) mRNA表达和AQP11免疫组化表达上调证实了这一点。ZnO-NPs的有益结果可能归因于通过抑制mTOR信号通路激活自噬。ZnO-NPs增强beclin-1和LC3 mRNA表达,降低p62 mRNA表达。ZnO-NPs还具有抗凋亡潜能(p53免疫表达降低)、抗炎和抗氧化作用[通过抑制血清环氧化酶-2 (COX-2)酶活性、组织核因子κ b (NF-κB)水平和血液缺氧诱导因子(HIF-1α)水平]。这些结果可能为DN的有效治疗指明了道路。Aquaporin11;BUN:血尿素氮;cox - 2: Cyclooxygenase-2;DAB: 3,3 '-二氨基联苯胺;DM:糖尿病;DN:糖尿病肾病;ELISA:酶联免疫吸附法;H&E:苏木精和伊红;HIF-1α:缺氧诱导因子;iNOS:诱导型一氧化氮合酶;LC3:微管相关蛋白1轻链3;mTOR:雷帕霉素的作用机制;NF-κB:核因子κ β;NPs:纳米粒子;PAS:周期性酸席夫;PCR:聚合酶链反应;PGE2:前列腺素E2;ROS:活性氧;STZ:链脲霉素;X±SEM:平均值±标准差;锌:锌;ZnO-NPs:氧化锌纳米颗粒。
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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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