Antioxidant activity of the organotellurium compound 3-[4-(N,N-dimethylamino)benzenetellurenyl]propanesulfonic acid against oxidative stress in synaptosomal membrane systems and neuronal cultures

Brain Res. 2001 Aug 17;911(1):12-21. doi: 10.1016/s0006-8993(01)02541-0.

Abstract

Antioxidant activities of 3-[4-(N,N-dimethylamino) benzenetellurenyl]propanesulfonic acid sodium salt (NDBT) were evaluated in solution, red blood cells, synaptosomal membranes, and cultured hippocampal neuronal cells after exposure to peroxynitrite (ONOO(-)) and hydroxyl radicals. The organotellurium compound NDBT possesses significant activity towards hydrogen peroxide and/or the hydroxyl radical in solution, demonstrated by inhibition of hydroxylation of terephthalic acid. In addition, the compound displayed great antioxidant abilities as shown by: reduction of ONOO(-)-induced 2,7-dichlorofluorescein (DCF) fluorescence in synaptosomes; complete prevention of lipid peroxidation in synaptosomes caused by OH radicals (TBARS), and significant prevention of protein oxidation caused by ONOO(-) and OH, indexed by the levels of protein carbonyls in synaptosomes and neuronal cells. The presence of the compound abolished neuronal cell death caused by ONOO(-). Further, the compound was effective in preventing the oxidative changes in synaptosomal membrane protein conformation and crosslinking (EPR spin labeling). Finally, the organotellurium molecule attenuated peroxynitrite-induced, luminol-dependent chemiluminescence in red blood cells--an index of cellular oxidation. These findings demonstrate the great potential of the antioxidant and are consistent with the notion that NDBT may have a role to play in modulating oxidative stress in neurodegenerative disorders, including Alzheimer's disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkanesulfonic Acids / pharmacology*
  • Animals
  • Antioxidants / pharmacology*
  • Cell Death / drug effects*
  • Cell Death / physiology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Free Radical Scavengers / pharmacology
  • Free Radicals / antagonists & inhibitors
  • Free Radicals / metabolism
  • Gerbillinae
  • Lipid Peroxidation / drug effects
  • Luminescent Measurements
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Nitrates / antagonists & inhibitors
  • Nitrates / pharmacology
  • Organometallic Compounds / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Tellurium*

Substances

  • 3-(4-(N,N-dimethylamino)benzenetellurenyl)propanesulfonic acid
  • Alkanesulfonic Acids
  • Antioxidants
  • Free Radical Scavengers
  • Free Radicals
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Nitrates
  • Organometallic Compounds
  • Reactive Oxygen Species
  • peroxynitric acid
  • propylsulfonic acid
  • Tellurium