title: Topical metal chelation therapy ameliorates oxidation-induced toxicity in diabetic cataract.
abstract: Oxidative stress plays a critical role in cataractogenesis, the leading cause of blindness worldwide. Since transition metals generate reactive oxygen species (ROS) formation, metal chelation therapy has been proposed for treatment of cataracts. However, the effectiveness of most chelators is limited by low tissue penetrability. This study is the first to demonstrate that the topically applied divalent metal chelator ethylenediamine tetraacetic acid (EDTA) combined with the carrier and permeability enhancer methyl sulfonyl methane (MSM) ameliorates both oxidation-induced lens opacification and the associated toxic accumulation of protein-4-hydroxynonenal (HNE) adducts. Both in vitro (rat lens culture) and in vivo (diabetic rats), EDTA-MSM (1) significantly reduced lens opacification by about 40-50%, (2) significantly diminished lens epithelial cell proliferation and fiber cell swelling in early stages of cataract formation in vivo, and (3) notably decreased the levels of protein-HNE adducts. These findings have important implications specifically for the treatment of cataract and generally for other diseases in which oxidative stress plays a key pathogenic role.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-0647, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shoeb
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Tianlin
authors.initials: T
authors.lastname: Xiao
authors.forename: Dale
authors.initials: D
authors.lastname: Hogan
authors.forename: Ira G
authors.initials: IG
authors.lastname: Wong
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Campbell
authors.forename: Naseem H
authors.initials: NH
authors.lastname: Ansari
mesh_terms: D000287:Administration, Topical; D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D002386:Cataract / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000379:methods*; D048909:Diabetes Complications / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008670:Metals / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013450:Sulfones / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000447:Aldehydes; D002614:Chelating Agents; D008670:Metals; D017382:Reactive Oxygen Species; D013450:Sulfones; D004492:Edetic Acid; C025910:dimethyl sulfone; C027576:4-hydroxy-2-nonenal; D004121:Dimethyl Sulfoxide