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DIBc nano metal-organic framework improves biochemical and pathological parameters of experimental chronic kidney disease.
Journal of Trace Elements in Medicine and Biology ( IF 3.6 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.jtemb.2020.126547
Saideh Fakharzadeh 1 , Hassan Argani 2 , Peyman Mohammadi Torbati 3 , Simin Dadashzadeh 4 , Somayeh Kalanaky 5 , Mohammad Hassan Nazaran 5 , Abbas Basiri 6
Affiliation  

Background

The growing morbidity and mortality rate of chronic kidney disease (CKD) has forced researchers to find more efficient strategies for controlling this disease. Studies have proven the important role of alteration in iron, zinc and selenium metabolism in CKD pathological process. Nanotechnology, through synthetizing nano metal-organic framework (NMOF) structures, can be employed as a valuable strategy for using these trace elements as the key for modification and improvement of CKD-related pathological events. After proving the anti-diabetic property of DIBc NMOF (which contains selenium and zinc) in the previous study, the impact of this NMOF on some important biochemical and pathological parameters of CKD was evaluated in the current study.

Methods

Knowing that diabetic nephropathy (DN) is the leading cause of CKD, male wistar rats were selected and given a high fat diet for 2 weeks and then were injected with streptozotocin (35 mg/kg) to induce DN. Six weeks after streptozotocin injection, DIBc or metformin treatment started and continued for 8 weeks.

Results

Eight weeks of DIBc treatment decreased plasma fasting blood glucose, blood urea nitrogen, uric acid, malondialdehyde (MDA) and HOMA-IR index compared to DN control and metformin groups. This NMOF significantly reduced urinary albumin excretion rate, MDA and 8-isoprostane, while it increased creatinine clearance in comparison to the above-mentioned groups. Renal histo-pathological images indicated that DIBc ameliorated glomerular basement membrane thickening and wrinkling, mesangial matrix expansion and hypercellularity and presence of intra-cytoplasmic hyaline droplets in proximal cortical tubules of kidney samples.

Conclusion

The results showed the therapeutic effect of DIBc on important biochemical and histo-pathological parameters of CKD, so this NMOF could be regarded as a promising novel anti-CKD agent.



中文翻译:


DIBc 纳米金属有机框架可改善实验性慢性肾病的生化和病理参数。


 背景


慢性肾脏病(CKD)的发病率和死亡率不断上升,迫使研究人员寻找更有效的策略来控制这种疾病。研究证明铁、锌、硒代谢的改变在CKD病理过程中发挥着重要作用。纳米技术通过合成纳米金属有机骨架(NMOF)结构,可以作为一种有价值的策略,利用这些微量元素作为修饰和改善 CKD 相关病理事件的关键。在前期研究中证明了DIBc NMOF(含有硒和锌)的抗糖尿病特性后,本研究评估了该NMOF对CKD一些重要生化和病理参数的影响。

 方法


已知糖尿病肾病(DN)是CKD的主要原因,选择雄性Wistar大鼠并给予高脂肪饮食2周,然后注射链脲佐菌素(35 mg/kg)以诱导DN。注射链脲佐菌素六周后,开始 DIBc 或二甲双胍治疗并持续 8 周。

 结果


与 DN 对照组和二甲双胍组相比,八周的 DIBc 治疗降低了血浆空腹血糖、血尿素氮、尿酸、丙二醛 (MDA) 和 HOMA-IR 指数。与上述组相比,该 NMOF 显着降低了尿白蛋白排泄率、MDA 和 8-异前列腺素,同时增加了肌酐清除率。肾脏组织病理学图像表明,DIBc 改善肾小球基底膜增厚和皱纹、系膜基质扩张和细胞增多以及肾脏样本近端皮质小管中细胞质内透明液滴的存在。

 结论


结果表明 DIBc 对 CKD 的重要生化和组织病理学参数具有治疗作用,因此该 NMOF 可以被视为一种有前途的新型抗 CKD 药物。

更新日期:2020-05-11
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