| Reactive oxygen species (ROS) are the sparks of the oxidative metabolism. Oxidative stress is the price we pay for using oxygen. ROS and reactive nitrogen species (RNS), such as superoxide, peroxide, hydroxyl radical, and peroxynitrite, are reactive and toxic, sometimes difficult to contain, but their production is important for regulation of metabolism, turnover of biomolecules and protection against microbial infection. ROS and RNS cause oxidative damage to all classes of biomolecules: proteins, lipids and DNA. There are a number of protective antioxidant mechanisms, including sequestration of redox-active metal ions, enzymatic inactivation of major ROS, inactivation of organic radicals by small molecules, such as GSH and vitamins, and, when all else fails, repair or turnover. Biomarkers of oxidative stress are readily detected in tissues in inflammation, and oxidative stress is increasingly implicated in the pathogenesis of chronic disease.
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- Review the evidence that atherosclerosis is an inflammatory disease initiated by production of ROS in the vascular wall.
- Discuss the evidence that hyperglycemia in diabetes induces a state of oxidative stress that leads to renal and vascular complications.
- Review the data on use of antioxidants in therapy for atherosclerosis and diabetes. Based on these studies, how strong is the evidence that these diseases are the result of increased oxidative stress? What are the limitations of these studies?
- Discuss recent advances in the use of antioxidants for tissue protection during cardiac surgery and transplantation.
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| Aliev G, Smith MA, Seyidov D et al. The role of oxidative stress in the pathophysiology of cerebrovascular lesions in Alzheimer's disease. Brain Pathol 2002;12:21-35.
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Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 2000;28:1708-1716.
Full article
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| Cracowski JL, Durand T, Bessard G. Isoprostanes as a biomarker of lipid peroxidation in humans: physiology, pharmacology and clinical implications. Trends Pharmacol Sci 2002;23:360-666.
Full article
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| Janero DR. Ischemic heart disease and antioxidants: mechanistic aspects of oxidative injury and its prevention. Crit Rev Food Sci Nutr 1995 Jan;35(1-2):65-81.
Full article
|
| Jollow DJ, McMillan DC. Oxidative stress, glucose-6-phosphate dehydrogenase and the red cell. Adv Exp Med Biol 2001;500:595-605.
|
| Koutsilieri E, Scheller C, Grunblatt E, Nara K, Li J, Riederer P. Free radicals in Parkinson's disease. J Neurol 2002;249 Suppl 2:1-5.
Full article
|
| Kuroki T, Isshiki K, King GL. Oxidative stress: the lead or supporting actor in the pathogenesis of diabetic complications. J Am Soc Nephrol 2003;14(Suppl 3):S216-220.
|
| Meagher EA. Treatment of atherosclerosis in the new millennium: is there a role for vitamin E? Prev Cardiol 2003;6:85-90.
|
| Nedeljkovic ZS, Gokce N, Loscalzo J. Mechanisms of oxidative stress and vascular dysfunction. Postgrad Med J 2003;79:195-199.
Full article
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| Roberts LJ 2nd, Morrow JD. Products of the isoprostane pathway: unique bioactive compounds and markers of lipid peroxidation. Cell Mol Life Sci 2002;59:808-820.
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