Controlling oxidative stress as a novel molecular approach to protecting the vascular wall in diabetes.
OBJECTIVE
In diabetes, oxidative stress plays a key role in the pathogenesis of vascular complications; therefore an antioxidant therapy would be of great interest in this disease.


RESULTS
Hyperglycemia directly promotes an endothelial dysfunction--inducing process of overproduction of superoxide at the mitochondrial level. This is the first and key event able to activate all the pathways involved in the development of vascular complications of diabetes. It has recently been shown that statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 blockers, calcium channel blockers, and thiazolidinediones have a strong intracellular antioxidant activity.


CONCLUSIONS
Classic antioxidants, such as vitamin E, failed to show beneficial effects on diabetic complications probably because their action is only "symptomatic". The preventive activity against hyperglycemia-induced oxidative stress shown by statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 blockers, calcium channel blockers, and thiazolidinediones justifies use of these compounds for preventing complications in patients with diabetes, in whom antioxidant defences have been shown to be defective.
Ceriello
Antonio
A
Warwick Medical School, Clinical Science Research Institute, University Hospital-Walsgrave Campus, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK. antonio.ceriello@warwick.ac.uk
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D045162:Thiazolidinediones / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D045162:Thiazolidinediones