title: Osmium tetroxide, used in the treatment of arthritic joints, is a fast mimic of superoxide dismutase.
abstract: Aqueous solutions of osmium tetroxide (OsO4) have been injected into arthritic knees for the past 45 years to chemically destroy diseased tissue, in a procedure termed "chemical synovectomy." Arthritis is an inflammatory disease. The primary inflammatory chemical species are the superoxide anion radical (O2.-) and nitric oxide (.NO), which combine to form the peroxynitrite anion (ONOO-). Here we show that OsO4 does not react with ONOO- but very efficiently catalyzes the dismutation of O2.- to O2 and H2O2. Using the pulse-radiolysis technique, the catalytic rate constant has been determined to be (1.43+/-0.04) x 10(9) M-1 s-1, independent of the pH in the 5.1-8.7 range. This value is about half that for the natural Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Per unit mass, OsO4 is about 60 times more active than Cu,Zn-SOD. The catalytically active couple is OsVIII/OsVII, OsVIII oxidizing O2.- to O2 with a bimolecular rate constant of k=(2.6+/-0.1)x10(9) M-1 s-1 and OsVII reducing it to H2O2 with a bimolecular rate constant of (1.0+/-0.1)x10(9) M-1 s-1. Although lower valent osmium species are intrinsically poor catalysts, they are activated through oxidation by O2.- to the catalytic OsVIII/OsVII redox couple. The OsVIII/OsVII catalyst is stable to biochemicals other than proteins and peptides comprising histidine, cysteine, and dithiols.
authors.affiliation: Department of Physical Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel. sarag@vms.huji.ac.il
authors.forename: Sara
authors.initials: S
authors.lastname: Goldstein
authors.forename: Gidon
authors.initials: G
authors.lastname: Czapski
authors.forename: Adam
authors.initials: A
authors.lastname: Heller
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D002384:Catalysis; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000627:therapeutic use; D009993:Osmium Tetroxide / Q000737:chemistry* / Q000627:therapeutic use; D030421:Peroxynitrous Acid / Q000737:chemistry; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D013481:Superoxides; D030421:Peroxynitrous Acid; D013482:Superoxide Dismutase; D009993:Osmium Tetroxide