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Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy
Diabetic nephropathy (DN) is one the most prevalent chronic complications of diabetes mellitus that affects as much as one-third of diabetic patients irrespective of the type of diabetes. Hyperglycemia is the key trigger for DN that initiates a number of microscopic and ultramicroscopic changes in k...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cureus
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699926/ https://www.ncbi.nlm.nih.gov/pubmed/26798569 http://dx.doi.org/10.7759/cureus.393 |
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author | Bhatti, Adnan Bashir Usman, Muhammad |
author_facet | Bhatti, Adnan Bashir Usman, Muhammad |
author_sort | Bhatti, Adnan Bashir |
collection | PubMed |
description | Diabetic nephropathy (DN) is one the most prevalent chronic complications of diabetes mellitus that affects as much as one-third of diabetic patients irrespective of the type of diabetes. Hyperglycemia is the key trigger for DN that initiates a number of microscopic and ultramicroscopic changes in kidney architecture. Microscopic changes include thickening of the glomerular basement membrane (GBM), tubular basement membrane (TBM), mesangial proliferation, arteriosclerosis, and glomerulotubular junction abnormalities (GTJA). Among the ultramicroscopic changes, effacement of podocytes and decrease in their density seem to be the centerpiece of DN pathogenesis. These changes in kidney architecture then produce functional deficits, such as microalbuminuria and decreased glomerular filtration rate (GFR). Among several mechanisms involved in inflicting damage to podocytes, injuries sustained by increased oxidative stress turns out to be the most important mechanism. Different variables that are included in increased production of reactive oxygen species (ROS) include a hyperglycemia-induced reduction in glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation via hyperglycemia, advanced glycation end products (AGEs), protein kinase C (PKC), and renin-angiotensin-aldosterone system (RAAS). Unfortunately, control of podocyte injury hasn’t received much attention as a treatment approach for DN. Therefore, this review article is mainly concerned with the exploration of various treatment options that might help in decreasing the podocyte injury, mainly by reducing the level of NADPH oxidase-mediated generation of ROS. This article concludes with a view that certain NADPH oxidase inhibitors, RAAS inhibitors, statins, antidiabetic drugs, and antioxidant vitamins might be useful in decreasing podocyte injury and resultant structural and functional kidney impairments in DN. |
format | Online Article Text |
id | pubmed-4699926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cureus |
record_format | MEDLINE/PubMed |
spelling | pubmed-46999262016-01-21 Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy Bhatti, Adnan Bashir Usman, Muhammad Cureus Internal Medicine Diabetic nephropathy (DN) is one the most prevalent chronic complications of diabetes mellitus that affects as much as one-third of diabetic patients irrespective of the type of diabetes. Hyperglycemia is the key trigger for DN that initiates a number of microscopic and ultramicroscopic changes in kidney architecture. Microscopic changes include thickening of the glomerular basement membrane (GBM), tubular basement membrane (TBM), mesangial proliferation, arteriosclerosis, and glomerulotubular junction abnormalities (GTJA). Among the ultramicroscopic changes, effacement of podocytes and decrease in their density seem to be the centerpiece of DN pathogenesis. These changes in kidney architecture then produce functional deficits, such as microalbuminuria and decreased glomerular filtration rate (GFR). Among several mechanisms involved in inflicting damage to podocytes, injuries sustained by increased oxidative stress turns out to be the most important mechanism. Different variables that are included in increased production of reactive oxygen species (ROS) include a hyperglycemia-induced reduction in glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation via hyperglycemia, advanced glycation end products (AGEs), protein kinase C (PKC), and renin-angiotensin-aldosterone system (RAAS). Unfortunately, control of podocyte injury hasn’t received much attention as a treatment approach for DN. Therefore, this review article is mainly concerned with the exploration of various treatment options that might help in decreasing the podocyte injury, mainly by reducing the level of NADPH oxidase-mediated generation of ROS. This article concludes with a view that certain NADPH oxidase inhibitors, RAAS inhibitors, statins, antidiabetic drugs, and antioxidant vitamins might be useful in decreasing podocyte injury and resultant structural and functional kidney impairments in DN. Cureus 2015-12-03 /pmc/articles/PMC4699926/ /pubmed/26798569 http://dx.doi.org/10.7759/cureus.393 Text en Copyright © 2015, Bhatti et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Internal Medicine Bhatti, Adnan Bashir Usman, Muhammad Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy |
title | Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy |
title_full | Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy |
title_fullStr | Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy |
title_full_unstemmed | Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy |
title_short | Drug Targets for Oxidative Podocyte Injury in Diabetic Nephropathy |
title_sort | drug targets for oxidative podocyte injury in diabetic nephropathy |
topic | Internal Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699926/ https://www.ncbi.nlm.nih.gov/pubmed/26798569 http://dx.doi.org/10.7759/cureus.393 |
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