Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bhatti, Adnan Bashir, Usman, Muhammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cureus 2015
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
_version_ 1782408252005285888
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
work_keys_str_mv AT bhattiadnanbashir drugtargetsforoxidativepodocyteinjuryindiabeticnephropathy
AT usmanmuhammad drugtargetsforoxidativepodocyteinjuryindiabeticnephropathy