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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.1016962023-07-03T07:50:41Z http://eprints.utm.my/id/eprint/101696/ Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat 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 NonPeerReviewed application/pdf en http://eprints.utm.my/id/eprint/101696/1/GhadaMohammadPFS2020.pdf Mohammad Alomari, Ghada (2020) Protective effect and action mechanism of gold and zincoxide nano-particles on early diabetic nephropathy in wistar rat. PhD thesis, Universiti Teknologi Malaysia, Faculty of Science. http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:146023
institution Universiti Teknologi Malaysia
building UTM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Teknologi Malaysia
content_source UTM Institutional Repository
url_provider http://eprints.utm.my/
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
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
publishDate 2020
url http://eprints.utm.my/id/eprint/101696/1/GhadaMohammadPFS2020.pdf
http://eprints.utm.my/id/eprint/101696/
http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:146023
_version_ 1770551080972713984
score 13.211869

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