Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats.
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.
Maitra
I
I
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Serbinova
E
E
Trischler
H
H
Packer
L
L
D000818:Animals; D019328:Buthionine Sulfoximine; D002386:Cataract / Q000139:chemically induced*; D005260:Female; D005609:Free Radicals; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007909:Lenses; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*
D005609:Free Radicals; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008063:Thioctic Acid; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione