Korean J Nephrol.  2003 May;22(3):285-293.

Effects of Advanced Glycation Endproducts (AGE) on Rat Glomerular Epithelial Cells (GEC): Roles of Reactive Oxygen Species (ROS)

• Ha TS
• Kim HS

Abstract

BACKGROUND
AGE-induced oxidative stress is implicated in the development and progression of diabetic nephropathy. AGE also affect the GEC to increase their permeability, therefore, we investigate the possibility that AGE may induce oxidative stress and subsequent injury to GEC. METHODS: We cultured rat GEC on the AGE- or BSA-coated plate with high glucose (HG) to produce more pathophysiologic conditions similar to prolonged diabetic environment in vivo and measured the change of ROS and their anti-oxidants systems. We also evaluated the effects of probucol as an antioxidant on this system. RESULTS: The amount of superoxide anion slightly decreased on AGE condition without significance. However, the production of hydrogen peroxide was significantly enhanced by 10% on AGE-coated and HG condition compared to control (BSA-coated and 5 mM glucose) (p< 0.05) and hydroxyl radical have also showed similar increase on AGE-coated and HG condition by 10% above control (p< 0.01), and both increases were attenuated by probucol (both, p< 0.05). The activity of superoxide dismutase (SOD) was decreased by 10% on AGE-coated and HG condition (p< 0.05) and recovered by probucol partially. However, there were no significant changes on the activity of other anti-oxidant enzymes including catalase, glutathione peroxidase, and glutathione reductase. Therefore, glomerular epithelial injury presenting proteinuria may be provoked by hydrogen peroxide and subsequently increased hydroxyl radical induced by AGE and high glucose. CONCLUSION: We might assume that superoxide had been converted to hydrogen peroxide by consumptive SOD in the presence of AGE, and subsequently produced hydroxyl radical, which could be reversed by anti-oxidant, may induce diabetic glomerular epithelial injury and eventually proteinuria.

Keyword

Diabetic nephropathy; Advanced glycation endproducts; Reactive oxygen species; Glomerular epithelial cells

MeSH Terms

Animals
Catalase
Diabetic Nephropathies
Epithelial Cells*
Glucose
Glutathione Peroxidase
Glutathione Reductase
Hydrogen Peroxide
Hydroxyl Radical
Oxidative Stress
Permeability
Probucol
Proteinuria
Rats*
Reactive Oxygen Species*
Superoxide Dismutase
Superoxides
Catalase
Glucose
Glutathione Peroxidase
Glutathione Reductase
Hydrogen Peroxide
Hydroxyl Radical
Probucol
Reactive Oxygen Species
Superoxide Dismutase
Superoxides