دورية أكاديمية
Zinc oxide nanoparticles prevent the onset of diabetic nephropathy by inhibiting multiple pathways associated with oxidative stress.
| العنوان: | Zinc oxide nanoparticles prevent the onset of diabetic nephropathy by inhibiting multiple pathways associated with oxidative stress. |
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| المؤلفون: | Padhye-Pendse A; Agharkar Research Institute, Pune, Maharashtra, India; Savitribai Phule Pune University, Pune, Maharashtra, India., Umrani R; L. M. College of Pharmacy, Ahmedabad, Gujarat, India., Paknikar K; Indian Institute of Technology, Bombay, India., Jadhav S; Agharkar Research Institute, Pune, Maharashtra, India., Rajwade J; Agharkar Research Institute, Pune, Maharashtra, India; Savitribai Phule Pune University, Pune, Maharashtra, India. Electronic address: jrajwade@aripune.org. |
| المصدر: | Life sciences [Life Sci] 2024 Jun 15; Vol. 347, pp. 122667. Date of Electronic Publication: 2024 Apr 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| مواضيع طبية MeSH: | Diabetic Nephropathies*/metabolism , Diabetic Nephropathies*/drug therapy , Diabetic Nephropathies*/prevention & control , Diabetic Nephropathies*/pathology , Oxidative Stress*/drug effects , Rats, Wistar* , Zinc Oxide*/pharmacology , Diabetes Mellitus, Experimental*/complications , Diabetes Mellitus, Experimental*/drug therapy , Diabetes Mellitus, Experimental*/metabolism, Animals ; Rats ; Male ; Nanoparticles ; Podocytes/drug effects ; Podocytes/metabolism ; Podocytes/pathology ; Fibrosis ; Kidney/drug effects ; Kidney/pathology ; Kidney/metabolism ; Streptozocin ; Signal Transduction/drug effects |
| مستخلص: | Background: Zinc deficiency is strongly correlated with prolonged diabetes mellitus and diabetic nephropathy (DN). Previously, glucose-lowering, insulinomimetic, and β-cell proliferative activities of zinc oxide nanoparticles (ZON) have been reported. Considering these pleiotropic effects, we hypothesized that ZON modulates multiple cellular pathways associated with necroptosis, inflammation, and renal fibrosis, which are involved in progressive loss of renal function. Aim: This study evaluated the effect of ZON on renal function, leading to the alleviation of DN in streptozotocin (STZ)-induced type 1 diabetic Wistar rats and proposed a probable mechanism for its activity. Methods: Wistar rats (n = 6/group) were used as healthy controls, diabetic controls, diabetic rats treated with ZON (1, 3, and 10 mg/kg), and insulin controls. Urine and serum biochemical parameters, glomerular filtration rate (GFR), and renal histology were also evaluated. Cultured E11 podocytes were evaluated in vitro for markers of oxidative stress, proteins associated with the loss of renal function, and genes associated with renal damage. Key Findings: STZ-treated rats receiving oral doses of ZON showed enhanced renal function, with no histological alterations in the kidney tissue. ZON inhibited the TGF-β/Samd3 pathway in renal fibrosis; blocked Ripk1/Ripk3/Mlkl mediated necroptosis and protected against hyperglycemia-induced pyroptosis. In E11 podocytes, ZON reduced oxidative stress under high glucose conditions and retained podocyte-specific proteins. Significance: A probable mechanism by which ZON prevents DN has been proposed, suggesting its use as a complementary therapeutic agent for the treatment of diabetic complications. To the best of our knowledge, this is the first study to demonstrate the in vitro effects of ZON in cultured podocytes. Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Diabetic nephropathy; E11 podocytes; Necroptosis; Pyroptosis; Renal fibrosis; Zinc oxide nanoparticles |
| المشرفين على المادة: | SOI2LOH54Z (Zinc Oxide) 5W494URQ81 (Streptozocin) |
| تواريخ الأحداث: | Date Created: 20240426 Date Completed: 20240510 Latest Revision: 20240510 |
| رمز التحديث: | 20240511 |
| DOI: | 10.1016/j.lfs.2024.122667 |
| PMID: | 38670449 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0631 |
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| DOI: | 10.1016/j.lfs.2024.122667 |