We have located links that may give you full text access.
Allopurinol protects human glomerular endothelial cells from high glucose-induced reactive oxygen species generation, p53 overexpression and endothelial dysfunction.
International Urology and Nephrology 2018 January
PURPOSE: Mitochondrial reactive oxygen species (ROS) overproduction in capillary endothelial cells is a prerequisite for the development of diabetic nephropathy. Inhibition of xanthine oxidase, another ROS generator, ameliorates experimental diabetic nephropathy. To test the hypothesis that the initial high glucose-induced ROS production by the mitochondria activates xanthine oxidase, which afterward remains as the major source of ROS, we cultured primary human glomerular endothelial cells (GEnC) under normal or high-glucose conditions, with or without the xanthine oxidase inhibitor allopurinol.
METHODS: ROS generation and nitric oxide synthase (NOS) activity were assessed by chemiluminescence or colorimetrically. Levels of intercellular adhesion molecule 1 (ICAM-1), p53 and phosphorylated p53 (p-p53) were assessed by western blotting.
RESULTS: Allopurinol prevented high glucose-induced ROS generation indicating that xanthine oxidase is the major source of ROS. Allopurinol protected GEnC from endothelial dysfunction since it prevented the high glucose-induced decrease in NOS activity and increase in ICAM-1 expression. Allopurinol reduced p53 and p-p53 levels induced by high glucose suggesting an axis of xanthine oxidase-derived ROS, DNA damage, p53 stabilization and endothelial dysfunction that may contribute to the pathogenesis of diabetic nephropathy.
CONCLUSIONS: Allopurinol protects GEnC from high glucose-induced ROS generation, p53 overexpression and endothelial dysfunction. These data provide a pathogenetic mechanism that supports the results of experimental and clinical studies about the beneficial effect of xanthine oxidase inhibitors on the development of diabetic nephropathy.
METHODS: ROS generation and nitric oxide synthase (NOS) activity were assessed by chemiluminescence or colorimetrically. Levels of intercellular adhesion molecule 1 (ICAM-1), p53 and phosphorylated p53 (p-p53) were assessed by western blotting.
RESULTS: Allopurinol prevented high glucose-induced ROS generation indicating that xanthine oxidase is the major source of ROS. Allopurinol protected GEnC from endothelial dysfunction since it prevented the high glucose-induced decrease in NOS activity and increase in ICAM-1 expression. Allopurinol reduced p53 and p-p53 levels induced by high glucose suggesting an axis of xanthine oxidase-derived ROS, DNA damage, p53 stabilization and endothelial dysfunction that may contribute to the pathogenesis of diabetic nephropathy.
CONCLUSIONS: Allopurinol protects GEnC from high glucose-induced ROS generation, p53 overexpression and endothelial dysfunction. These data provide a pathogenetic mechanism that supports the results of experimental and clinical studies about the beneficial effect of xanthine oxidase inhibitors on the development of diabetic nephropathy.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app