Oxidative stress represents one of the most important factors involved in the pathogenesis of endothelial dysfunction during diabetes and is characterized by an elevation of ROS as a consequence of increased free radicals production and/or reduced antioxidant systems. Diabetes mellitus has been associated with increased formation of free radicals and reduced concentrations of superoxide dismutase, catalase, glutathione, and ascorbic acid. The increased oxidative stress observed in diabetes may be due to different mechanisms, such as glucose autoxidation, PKC activation, AGE generation, increased availability of substrates through the polyol pathway, and enhanced eicosanoid metabolism. Therefore, free radicals may alter endothelium-dependent vasodilatation by inhibiting NO or behaving as an endothelium-derived constricting factor. Several studies have shown that administration of antioxidant enzymes also in combination may improve or restore the impaired endothelium-dependent response in diabetes and during high glucose exposure. However, other studies demonstrated that superoxide dismutase had less effect or no effect in improving endothelium-dependent vasodilatation compared to hydroxyl radical scavengers; therefore, hydroxyl radicals are thought to be more important in eliciting endothelial dysfunction.
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