Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat

Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and has become a global health issue. Recently, nanomedicines have attracted the attention of researchers; gold nanoparticles (AuNPs) and zinc oxide nanoparticles (ZnONPs) were demonstrated to have antihyperglycemic and antiox...

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Main Author:	Mohammad Alomari, Ghada
Format:	Thesis
Language:	English
Published:	2020
Subjects:	Q Science (General)
Online Access:	http://eprints.utm.my/id/eprint/101696/1/GhadaMohammadPFS2020.pdf
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spelling	my-utm-ep.1016962023-07-03T07:50:41Z Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat 2020 Mohammad Alomari, Ghada Q Science (General) Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and has become a global health issue. Recently, nanomedicines have attracted the attention of researchers; gold nanoparticles (AuNPs) and zinc oxide nanoparticles (ZnONPs) were demonstrated to have antihyperglycemic and antioxidative effects. This study aimed to explore the renoprotective effects of AuNPs and ZnONPs, and to identify the potential mechanisms of action in animal model of DN. Following induction of diabetes using a single dose of streptozotocin, 30 adult male rats were divided into three groups: 10 diabetic, 10 diabetic treated intraperitoneally for seven weeks with synthesised AuNP (51.8 ± 0.7 nm, 2.5 mg/kg/day), and 10 diabetic treated intraperitoneally with commercial ZnONP (<100 nm, 2.5 mg/kg/day). 10 non-diabetic rats were used as control. Pathohistological, biochemical, and molecular studies were performed to achieve the goals of this research. Diabetic animals treated with AuNPs exhibited significant reductions in blood glucose levels, urine albumin excretion, creatinine clearance, and blood urea nitrogen. The levels of oxidative stress markers: catalase, superoxide dismutase, and malondialdehyde were restored significantly evidence of antioxidant effect of AuNPs. Ultrastructural and histological findings highlighted the protective efficacy of AuNPs to reduce pathohistological hallmarks of DN, including glomerular basement membrane thickening, podocyte injury and glomerular sclerosis. Results from this study suggested that the protection against the development of DN was attributed to antioxidant and antihyperglycemic function of AuNPs. Both functions significantly reduced inflammation, fibrosis, and angiogenesis via the downregulation of tumor necrosis factor-a, transforming growth factor-ß, and vascular endothelial growth factor-A. AuNP treatment also activated matrix metalloproteinase, which reduces the accumulation of extracellular matrix proteins, collagen IV, and fibronectin. Treatment also restored the expression of nephrin and podocin, which protects against podocyte injury. Equally, ZnONP treatment prevented the increase of blood glucose, urine albumin excretion, creatinine clearance, and blood urea nitrogen. Significant increases in oxidative stress markers (catalase and superoxide dismutase) and a reduction of malondialdehyde also indicated antioxidative effects of ZnONPs. Early histological hallmarks of DN (e.g., glomerular basement membrane thickening, podocyte injury, and glomerular sclerosis) were also reduced by ZnONP treatment. ZnONP treatment also significantly downregulated tumor necrosis factor-a, transforming growth factor-ß, and vascular endothelial growth factor-A, but upregulated matrix metalloproteinase. The factors described above attenuated the hallmarks of DN while reducing the accumulation of extracellular matrix proteins, collagen IV, and fibronectin, thus preventing the progress of DN. Moreover, the expression of nephrin and podocin proteins, which protect against podocyte injury and albumin leakage in urine, was restored to normal levels. These results showed that AuNP and ZnONP have renoprotective effects against the development of DN via their antihyperglycemic, antioxidative, antiinflammatory, antifibrotic, and antiangiogenic effects. 2020 Thesis http://eprints.utm.my/id/eprint/101696/ http://eprints.utm.my/id/eprint/101696/1/GhadaMohammadPFS2020.pdf application/pdf en public http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:146023 phd doctoral Universiti Teknologi Malaysia, Faculty of Science Faculty of Science
institution	Universiti Teknologi Malaysia
collection	UTM Institutional Repository
language	English
topic	Q Science (General)
spellingShingle	Q Science (General) Mohammad Alomari, Ghada Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat
description	Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and has become a global health issue. Recently, nanomedicines have attracted the attention of researchers; gold nanoparticles (AuNPs) and zinc oxide nanoparticles (ZnONPs) were demonstrated to have antihyperglycemic and antioxidative effects. This study aimed to explore the renoprotective effects of AuNPs and ZnONPs, and to identify the potential mechanisms of action in animal model of DN. Following induction of diabetes using a single dose of streptozotocin, 30 adult male rats were divided into three groups: 10 diabetic, 10 diabetic treated intraperitoneally for seven weeks with synthesised AuNP (51.8 ± 0.7 nm, 2.5 mg/kg/day), and 10 diabetic treated intraperitoneally with commercial ZnONP (<100 nm, 2.5 mg/kg/day). 10 non-diabetic rats were used as control. Pathohistological, biochemical, and molecular studies were performed to achieve the goals of this research. Diabetic animals treated with AuNPs exhibited significant reductions in blood glucose levels, urine albumin excretion, creatinine clearance, and blood urea nitrogen. The levels of oxidative stress markers: catalase, superoxide dismutase, and malondialdehyde were restored significantly evidence of antioxidant effect of AuNPs. Ultrastructural and histological findings highlighted the protective efficacy of AuNPs to reduce pathohistological hallmarks of DN, including glomerular basement membrane thickening, podocyte injury and glomerular sclerosis. Results from this study suggested that the protection against the development of DN was attributed to antioxidant and antihyperglycemic function of AuNPs. Both functions significantly reduced inflammation, fibrosis, and angiogenesis via the downregulation of tumor necrosis factor-a, transforming growth factor-ß, and vascular endothelial growth factor-A. AuNP treatment also activated matrix metalloproteinase, which reduces the accumulation of extracellular matrix proteins, collagen IV, and fibronectin. Treatment also restored the expression of nephrin and podocin, which protects against podocyte injury. Equally, ZnONP treatment prevented the increase of blood glucose, urine albumin excretion, creatinine clearance, and blood urea nitrogen. Significant increases in oxidative stress markers (catalase and superoxide dismutase) and a reduction of malondialdehyde also indicated antioxidative effects of ZnONPs. Early histological hallmarks of DN (e.g., glomerular basement membrane thickening, podocyte injury, and glomerular sclerosis) were also reduced by ZnONP treatment. ZnONP treatment also significantly downregulated tumor necrosis factor-a, transforming growth factor-ß, and vascular endothelial growth factor-A, but upregulated matrix metalloproteinase. The factors described above attenuated the hallmarks of DN while reducing the accumulation of extracellular matrix proteins, collagen IV, and fibronectin, thus preventing the progress of DN. Moreover, the expression of nephrin and podocin proteins, which protect against podocyte injury and albumin leakage in urine, was restored to normal levels. These results showed that AuNP and ZnONP have renoprotective effects against the development of DN via their antihyperglycemic, antioxidative, antiinflammatory, antifibrotic, and antiangiogenic effects.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Mohammad Alomari, Ghada
author_facet	Mohammad Alomari, Ghada
author_sort	Mohammad Alomari, Ghada
title	Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat
title_short	Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat
title_full	Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat
title_fullStr	Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat
title_full_unstemmed	Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat
title_sort	protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat
granting_institution	Universiti Teknologi Malaysia, Faculty of Science
granting_department	Faculty of Science
publishDate	2020
url	http://eprints.utm.my/id/eprint/101696/1/GhadaMohammadPFS2020.pdf
_version_	1776100750121762816

Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat

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