Jakus V
Dpt of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Sasinkova 2, SK-811 08 Bratislava, Slovakia.
Bratisl Lek Listy. 2000;101(10):541-51.
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.)
最近的实验结果表明，在糖尿病控制不佳的患者中，活性氧和氮物种（ROS/RNS）的过度产生、抗氧化防御能力降低以及酶促途径的改变会导致内皮、血管和神经血管功能障碍。在过去十年中，人们对氧化应激及其在糖尿病发生、糖尿病并发症发展、动脉粥样硬化和相关心血管疾病中的潜在作用产生了浓厚兴趣。氧化应激的后果包括对DNA、脂质、蛋白质的损伤，细胞内稳态的破坏以及受损分子的积累。本综述总结了关于ROS/RNS在血管氧化应激和美拉德反应发病机制方面的最新知识。有证据表明，美拉德反应在衰老和糖尿病中是氧化损伤的放大器。此外，还讨论了抗氧化系统和抗氧化药物治疗在糖尿病治疗中的实验观察结果。这些数据表明，通过特定抗氧化剂或联合药物制剂针对糖尿病患者的特定大分子、组织和器官进行靶向治疗，可能成为一种相关的辅助药物治疗方法，可改善血糖控制、血压控制和血脂异常管理，以治疗或预防糖尿病微血管和大血管并发症的进展。补充抗氧化剂作为一种有前景的辅助治疗方法，可在糖尿病中发挥有益作用。一些抗糖尿病药物可能具有抗氧化特性，而与它们对血糖控制的主要作用无关。目前，多个实验室正在深入研究晚期糖基化终产物（AGEs）形成抑制剂在延缓糖尿病并发症方面的治疗潜力。此外，准确、灵敏的糖尿病氧化损伤早期检测方法的开发，对于抗氧化剂干预的功能结果也很重要。（表6，图3，参考文献117。）
