Oxidative stress hyperglycemia

What is evident is that the study of hyperglycemia and the glycation theory has now extended to that of oxidative stress. Hyperglycemia may make a modest contribution to this stress, although other sources, such as transition metal overload and increased oxidation of other reducing agents such as ascorbic acid seem more likely candidates. 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Hyperglycemia-induced enhanced oxidative stress has also been reported in cultured VSMC and different tissues from STZ-diabetic rats (Baynes and Thorpe 1999 Baynes 1991 Cai and Harrison 2000). In addition, the contribution of enhanced production of superoxide anion (02 ) in the decreased expression of Gia proteins has recently been reported in aortic VSMC from STZ-diabetic rats and A10 cells exposed to high glucose (Li et al. 2008). Antioxidants such as a-tocopherol and NAC—scavengers of 02 —and DPI (an inhibitor of NADPH oxidase) that restored the enhanced levels of O2- induced by hyperglycemia also restored the hyperglycemia-induced decreased expression of Gia-2 and Gia-3 to control levels (Li et al. 2008). These studies implicate NADPH oxidase/C>2 in... 

Fig. 9.2 Schematic diagram depicting the possible mechanisms by which hyperglycemia/diabetes decreases the expression of Gia proteins and adenylyl cyclase signaling. Diabetes/hyperglycemia augments the levels of vasoactive peptides including Ang II/ET-1 that enhance the oxidative stress by increasing the levels of superoxide anion (O2 ) and peroxynitrite (ONOO ). O2 and ONOO-decrease the levels of Gi proteins.The treatment with antioxidants and ONOO- scavengers reverses the hyperglycemia-induced decreased expression of Gia proteins and adenylyl cyclase signaling.

Monnier, L., E. Mas, C. Ginet, F. Michel, L. Villon, J.P. Cristol, and C. Colette. 2006. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295 1681-1687. 

Kamada H, Yu F, Nito C, Chan PH (2007) Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after foctil cerebial ischemia/repeifusion in rats relation to blood-brain barrier dysfunction. Stroke 38 1044-1049... 

Ceriello A, dello Russo P, Amstad P, Cerutti P. High glucose induces antioxidant enzymes in human endothelial cells in culture. Evidence linking hyperglycemia and oxidative stress. Diabetes 1996 45 471 77. 

Otsyula, M., M. S. King, T. G. Ketcham, R. A. Sanders, and J. B. Watkins. 2003. Oxidative stress in rats after 60 days of hypergalactosemia or hyperglycemia. International Journal of Toxicology 22 423 27. 

Lau, Y. S., Tian, X. Y., Huang, Y., Murugan, D., Achike, F.I., Mustafa, M.R. (2013). Boldine protects endothelial function in hyperglycemia -induced oxidative stress through an antioxidant mechanism. Biochem. Pharmacol, 85(3), 367-375. 

In diabetes, hyperglycemia is associated with an excessive oxidative stress leading to cell death in endothelial cells. In an animal model of streptozotocin-induced diabetes, CORM-3 decreased urinary 8-epi-isoprotane PGF (2a), reduced endothelial cell sloughing, and restored vascular function, likely by limiting oxidative stress [67,68]. 

Brouwers O, Niessen PM, Ferreira I, Miyata T, Scheffer PG, Teerlink T, Schrauwen P, Brownlee M, Stehouwer CD, and Schalkwijk CG. Overexpression of glyoxalase-1 reduces hyperglycemia-induced levels of advanced glycation end products and oxidative stress in diabetic rats. J Biol Chem, 286 1374-1380 (2011). 

Hyperglycemia-induced oxidative stress has an important role in the pathogenesis of diabetic complications. Human monocytes exposed to 2-deoxy-D-ribose exhibited loss of cell viability, overproduction of ROS, depletion of glutathione, and apoptosis. Treatment with PLP inhibited these as well as lipid peroxidation and protein oxidation (4). Pyridoxine has a very high level of quenching of hydroxyl radicals (5). Mono- and bicyclic amino pyridinols have been synthesized from pyridoxine hydrochloride and have been shown to have antioxidant properties (6). 

There is increased reactive carbonyl compound (RCO) with attendant protein modification (carbonyl stress) in atherosclerosis carbonyl stress might be derived from hyperglycemia (and lipedemia), oxidative stress, and/or impaired detoxification of RCO (423). 

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