Oxidative stress and diabetes-associated complications.
OBJECTIVE
To review the role of oxidative stress in the development of complications of diabetes.


METHODS
Evidence that implicates hyperglycemia-derived oxygen free radicals as mediators of diabetes-associated complications is presented and discussed.


RESULTS
Recent studies have indicated that a hyperglycemia-induced overproduction of superoxide seems to be the first and main event in the activation of all pathways involved in the pathogenesis of complications of diabetes. Superoxide overproduction is accompanied by increased generation of nitric oxide and, consequently, formation of the strong oxidant peroxynitrite and by poly(adenosine diphosphate-ribose) polymerase activation, which in turn further activates the pathways involved in the pathogenesis of diabetes-related complications. This process results in acute endothelial dysfunction and activation of inflammation in blood vessels of patients with diabetes, and these factors contribute to the development of complications of diabetes.


CONCLUSIONS
In vivo evidence supports the major contribution of hyperglycemia in producing oxidative stress and, ultimately, acute endothelial dysfunction in blood vessels of patients with diabetes.
Ceriello
Antonio
A
Department of Pathology and Medicine, Experimental and Clinical and Chair of Internal Medicine, University of Udine, Italy.
D048909:Diabetes Complications; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007249:Inflammation; D009569:Nitric Oxide; D018384:Oxidative Stress; D013481:Superoxides
D013481:Superoxides; D009569:Nitric Oxide