title: Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.
abstract: This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.
authors.affiliation: Department of Food and Nutrition, Japan Women's University, Tokyo, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nagai
authors.forename: David B
authors.initials: DB
authors.lastname: Murray
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.forename: John W
authors.initials: JW
authors.lastname: Baynes
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use*; D048909:Diabetes Complications / Q000188:drug therapy*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002614:Chelating Agents; D017127:Glycation End Products, Advanced; D000449:Aldehyde Reductase