Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury
Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damag...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2017/8379327 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849695798736977920 |
|---|---|
| author | Selim Fakhruddin Wael Alanazi Keith E. Jackson |
| author_facet | Selim Fakhruddin Wael Alanazi Keith E. Jackson |
| author_sort | Selim Fakhruddin |
| collection | DOAJ |
| description | Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure. |
| format | Article |
| id | doaj-art-ce95dc217e144ee58f7a7a9d3776038d |
| institution | DOAJ |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-ce95dc217e144ee58f7a7a9d3776038d2025-08-20T03:19:39ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/83793278379327Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal InjurySelim Fakhruddin0Wael Alanazi1Keith E. Jackson2Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe (ULM), Pharmacy Building, 1800 Bienville Dr., Monroe, LA 71201, USADepartment of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe (ULM), Pharmacy Building, 1800 Bienville Dr., Monroe, LA 71201, USADepartment of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe (ULM), Pharmacy Building, 1800 Bienville Dr., Monroe, LA 71201, USADiabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure.http://dx.doi.org/10.1155/2017/8379327 |
| spellingShingle | Selim Fakhruddin Wael Alanazi Keith E. Jackson Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury Journal of Diabetes Research |
| title | Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury |
| title_full | Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury |
| title_fullStr | Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury |
| title_full_unstemmed | Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury |
| title_short | Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury |
| title_sort | diabetes induced reactive oxygen species mechanism of their generation and role in renal injury |
| url | http://dx.doi.org/10.1155/2017/8379327 |
| work_keys_str_mv | AT selimfakhruddin diabetesinducedreactiveoxygenspeciesmechanismoftheirgenerationandroleinrenalinjury AT waelalanazi diabetesinducedreactiveoxygenspeciesmechanismoftheirgenerationandroleinrenalinjury AT keithejackson diabetesinducedreactiveoxygenspeciesmechanismoftheirgenerationandroleinrenalinjury |