title: Advanced glycation endproducts (AGEs): Pharmacological inhibition in diabetes.
abstract: AGE inhibitors may act by various mechanisms at different steps of advanced glycation endproduct (AGE) formation (depending on oxidative stress and/or carbonyl stress) and AGE-mediated damage: trapping of reactive dicarbonyl species; antioxidant activity by transition metal chelation; other antioxidant activity including free radical scavenging; AGE cross-link breaking; AGE receptor (RAGE) blocking; RAGE signaling blocking; glycemia reduction by anti-diabetic therapy; aldose reductase inhibition; shunting of trioses-P towards the pentose-P pathway by transketolase activation. Most of the inhibitors have several sites of action. Practically one can distinguish drugs specifically developed as AGE inhibitors or AGE breakers; RAGE and receptor signaling blockers; other therapeutic compounds which were found subsequently to possess also AGE inhibitor activity, including dietary antioxidants. Encouraging results obtained in studies of various AGE inhibitors, conducted in vitro and in diabetic animals, are summarized in this review. However most of the clinical trials have been more or less disappointing, in part because of side effects; the long-term therapeutic interest of the most recently developed AGE inhibitors or breakers remains to be demonstrated in diabetes.
authors.affiliation: Equipe de recherche Protéines Modifiées, Protéases et Physiopathologie de l'Endothélium Vasculaire, laboratoire de pharmacologie, faculté de pharmacie, université Paris-V, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Peyroux
authors.forename: M
authors.initials: M
authors.lastname: Sternberg
mesh_terms: D003432:Cross-Linking Reagents; D003920:Diabetes Mellitus / Q000503:physiopathology*; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D006801:Humans; D015416:Maillard Reaction
chemical_list: D003432:Cross-Linking Reagents; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced