The preventive anti-oxidant action of thiazolidinediones: a new therapeutic prospect in diabetes and insulin resistance.
BACKGROUND
Hyperglycaemia-derived oxygen free radicals may be mediators of diabetic complications.


METHODS
Recent studies show that hyperglycaemia-induced overproduction of superoxide seems to be the first and key event in activation of pathways involved in the pathogenesis of diabetic complications. Superoxide overproduction is accompanied by increased nitric oxide generation and consequently formation of the powerful oxidant peroxynitrite and by poly(ADP-ribose) polymerase activation. This results in acute endothelial dysfunction and activation of inflammation in blood vessels that contribute to the development of diabetic complications.


RESULTS
Thiazolidinediones are a new class of insulin-sensitizing agents. They inhibit intracellular free radical overproduction. In particular, they inhibit the same pathways involved in hyperglycaemia-derived oxidative stress, particularly iNOS and NF-kappaB. Studies in animal models suggest that thiazolidinediones can reduce oxidative stress, independent of their ability to reduce hyperglycaemia.


CONCLUSIONS
The availability of compounds that simultaneously decrease hyperglycaemia, restore insulin resistance and inhibit pathways activated by high glucose producing oxidative stress signals a promising approach.
Da Ros
R
R
Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Piazzale S. Maria della Misericordia, 33100 Udine, Italy.
Assaloni
R
R
Ceriello
A
A
D000975:Antioxidants / Q000627:therapeutic use*; D048909:Diabetes Complications / Q000517:prevention & control*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007333:Insulin Resistance; D018384:Oxidative Stress / Q000187:drug effects; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000975:Antioxidants; D045162:Thiazolidinediones