title: Clinical potential of advanced glycation end-product inhibitors in diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Clinical Sciences, Division of Nephrology, University of Rome La Sapienza, Rome, Italy. Paolo.Mene@uniroma1.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Menè
authors.forename: Francescaromana
authors.initials: F
authors.lastname: Festuccia
authors.forename: Francesco
authors.initials: F
authors.lastname: Pugliese
mesh_terms: D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000097:blood; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans
chemical_list: D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine