Menè Paolo, Festuccia Francescaromana, Pugliese Francesco
Department of Clinical Sciences, Division of Nephrology, University of Rome La Sapienza, Rome, Italy.
Am J Cardiovasc Drugs. 2003;3(5):315-20. doi: 10.2165/00129784-200303050-00002.
Non-enzymatic accumulation of advanced glycation end-products (AGE) is to some extent a physiologic consequence of tissue aging. On the other hand, circulating AGE and tissue deposits mark the course of diabetes mellitus as well as a variety of other vascular or degenerative diseases. AGE generation is paralleled by oxidative damage and lipid peroxidation within target tissue, with features of inflammation through the involvement of monocytes/macrophages expressing receptors for glycated macromolecules. Over the past 15 years, a wealth of data concerning the pharmacology of AGE have been gathered through animal and human investigations, targeting their likely contribution to the progression of diabetic and non-diabetic vascular damage. Several agents have been shown to interfere with the formation of AGE or AGE precursors, bind to tissue receptors, or promote breakdown of deposits. The first and most studied inhibitor, aminoguanidine, has shown extensive beneficial effects in experimental models of diabetic vascular damage, recently entering phase I-III clinical investigation. Newer anti-AGE agents include pyridoxamine and the so-called 'amadorins', cross-link breakers, AGE binders and receptor antagonists.
晚期糖基化终产物（AGE）的非酶促积累在一定程度上是组织衰老的生理结果。另一方面，循环中的AGE和组织沉积物标志着糖尿病以及多种其他血管性或退行性疾病的病程。在靶组织中，AGE的生成与氧化损伤和脂质过氧化同时发生，通过表达糖基化大分子受体的单核细胞/巨噬细胞参与而具有炎症特征。在过去15年中，通过动物和人体研究收集了大量关于AGE药理学的数据，针对它们可能对糖尿病和非糖尿病血管损伤进展的影响。已显示几种药物可干扰AGE或AGE前体的形成、与组织受体结合或促进沉积物的分解。第一种也是研究最多的抑制剂氨基胍，在糖尿病血管损伤的实验模型中显示出广泛的有益作用，最近已进入I - III期临床研究。新型抗AGE药物包括吡哆胺和所谓的“阿马多林”、交联断裂剂、AGE结合剂和受体拮抗剂。
