The role of free radicals, oxidative stress and antioxidant systems in diabetic vascular disease.
Recent experimental findings suggest that overproduction of reactive oxygen and nitrogen species (ROS/RNS), lowered antioxidant defense and alterations of enzymatic pathways in humans with poorly controlled diabetes mellitus can contribute to endothelial, vascular and neurovascular dysfunction. Over the past decade, there has been substantial interest in oxidative stress and its potential role in diabetogenesis, development of diabetic complications, atherosclerosis and associated cardiovascular disease. Consequences of oxidative stress are damage to DNA, lipids, proteins, disruption in cellular homeostasis and accumulation of damaged molecules. This review summarizes recent knowledge on the pathomechanism of ROS/RNS in vascular oxidative stress and Maillard reactions. Evidence suggests that Maillard reactions act as amplifier of oxidative damage in aging and diabetes. Furthermore, results of experimental observations with antioxidant systems and antioxidant pharmacotherapy in the treatment of diabetes mellitus are discussed. These data indicate that the targeting therapy to specific macromolecules, tissues and organs of diabetics by specific antioxidants or combined drug preparates could become a relevant adjuvant pharmacotherapy with improved glycaemic control, blood pressure control and management of dyslipidemia for the treatment or prevention of progression of micro- and macrovascular diabetic complications. Supplementation with antioxidants as a promising complementary treatment can exert beneficial effects in diabetes. Some antidiabetic drugs may have antioxidant properties independently of their main role on glycaemia control. Therapeutic potential of inhibitors of AGEs formation for delaying of diabetic complications is now intensively studied in several laboratories. Furthermore, for functional outcomes of the intervention with antioxidants is also important development of accurate and sensitive methods for early detection of oxidative damage in diabetes. (Tab. 6, Fig. 3, Ref. 117.)
Jakus
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Dpt of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Sasinkova 2, SK-811 08 Bratislava, Slovakia. Jakus@post.sk
D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species