Tempol-H inhibits opacification of lenses in organ culture

Free Radic Biol Med. 2003 Nov 15;35(10):1194-202. doi: 10.1016/s0891-5849(03)00505-7.

Abstract

Cataract is the world's leading cause of blindness and a disease for which no efficacious medical therapy is available. To screen potential anti-cataract agents, a lens organ culture model system was used. Opacification of lenses maintained in culture was induced by specific insults including H(2)O(2) or the cataractogenic sugar xylose. Potential anti-cataract agents were added to the culture medium and their ability to inhibit opacification and certain biochemical changes associated with the opacification were assessed. Among the compounds tested, Tempol-H, the hydroxylamine of the nitroxide Tempol, gave the most promising results. It significantly inhibited opacification of rat lenses in an H(2)O(2)-induced cataract system as well as opacification of rhesus monkey lenses induced by xylose. Tempol-H inhibited the loss of glutathione, the leakage of protein, and decreases in the ability of cultured lenses to accumulate (3)H-choline from the medium, all of which were associated with the development of lens opacification. The antioxidative activity of Tempol-H and its ability to re-dox cycle make it an attractive candidate as a therapeutic agent for the prevention of aging-related cataract.

MeSH terms

  • Animals
  • Cataract / chemically induced
  • Cataract / metabolism
  • Cataract / prevention & control*
  • Cattle
  • Choline / metabolism
  • Cyclic N-Oxides / therapeutic use*
  • Female
  • Glutathione / metabolism
  • Hydrogen Peroxide / toxicity
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Macaca mulatta
  • Male
  • Organ Culture Techniques
  • Oxidants / toxicity
  • Oxidation-Reduction
  • Rats
  • Rats, Sprague-Dawley
  • Spin Labels
  • Xylose / toxicity

Substances

  • Cyclic N-Oxides
  • Oxidants
  • Spin Labels
  • Xylose
  • Hydrogen Peroxide
  • Glutathione
  • Choline
  • tempol