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Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats.

Abstract
We investigated the effect of alpha-lipoic acid, a powerful antioxidant, on cataract formation in L-buthionine(S,R)-sulfoximine (BSO)-treated newborn rats and found that a dose of 25 mg/kg b.w. protected 60% of animals from cataract formation. L-buthionine(S,R)-sulfoximine is an inhibitor of glutathione synthesis, whose administration to newborn animals leads to the development of cataracts; this is a potential model for studying the role of therapeutic antioxidants in protecting animals from cataract formation. Major biochemical changes in the lens associated with the protective effect of alpha-lipoic acid were increases in glutathione, ascorbate, and vitamin E levels, loss of which are effects of BSO administration. Treatment with alpha-lipoic acid also restored the activities of glutathione peroxidase, catalase, and ascorbate free radical reductase in lenses of L-buthionine(S,R)-sulfoximine-treated animals but did not affect glutathione reductase or superoxide dismutase activity. We conclude that alpha-lipoic acid may take over some of the functions of glutathione (e.g., maintaining the higher level of ascorbate, indirect participation in vitamin E recycling); the increase of glutathione level in lens tissue mediated by lipoate could be also due to a direct protection of protein thiols. Thus, alpha-lipoic acid could be of potential therapeutic use in preventing cataracts and their complications.
AuthorsI Maitra, E Serbinova, H Trischler, L Packer
JournalFree radical biology & medicine (Free Radic Biol Med) Vol. 18 Issue 4 Pg. 823-9 (Apr 1995) ISSN: 0891-5849 [Print] United States
PMID7750805 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Free Radicals
  • Methionine Sulfoximine
  • Buthionine Sulfoximine
  • Thioctic Acid
  • Glutamate-Cysteine Ligase
  • Glutathione
Topics
  • Animals
  • Buthionine Sulfoximine
  • Cataract (chemically induced)
  • Female
  • Free Radicals
  • Glutamate-Cysteine Ligase (antagonists & inhibitors, pharmacology)
  • Glutathione (pharmacology)
  • Humans
  • Infant, Newborn
  • Lenses
  • Male
  • Methionine Sulfoximine (analogs & derivatives, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Thioctic Acid (pharmacology)

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