title: Stereospecific effects of R-lipoic acid on buthionine sulfoximine-induced cataract formation in newborn rats.
abstract: This study revealed a marked stereospecificity in the prevention of buthionine sulfoximine-induced cataract, and in the protection of lens antioxidants, in newborn rats by alpha-lipoate, R- and racemic alpha-lipoate decreased cataract formation from 100% (buthionine sulfoximine only) to 55% (buthionine sulfoximine + R-alpha-lipoic acid) and 40% (buthionine sulfoximine + rac-alpha-lipoic acid) (p<0.05 compared to buthionine sulfoximine only). S-alpha-lipoic acid had no effect on cataract formation induced by buthionine sulfoximine. The lens antioxidants glutathione, ascorbate, and vitamin E were depleted to 45, 62, and 23% of control levels, respectively, by buthionine sulfoximine treatment, but were maintained at 84-97% of control levels when R-alpha-lipoic acid or rac-alpha-lipoic acid were administered with buthionine sulfoximine; S-alpha-lipoic acid administration had no protective effect on lens antioxidants. When enantiomers of alpha-lipoic acid were administered to animals, R-alpha-lipoic acid was taken up by lens and reached concentrations 2- to 7-fold greater than those of S-alpha-lipoic acid, with rac-alpha-lipoic acid reaching levels midway between the R-isomer and racemic form. Reduced lipoic acid, dihydrolipoic acid, reached the highest levels in lens of the rac-alpha-lipoic acid-treated animals and the lowest levels in S-alpha-lipoic acid-treated animals. These results indicate that the protective effects of alpha-lipoic acid against buthionine sulfoximine-induced cataract are probably due to its protective effects on lens antioxidants, and that the stereospecificity exhibited is due to selective uptake and reduction of R-alpha-lipoic acid by lens cells.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3200, USA.
authors.forename: I
authors.initials: I
authors.lastname: Maitra
authors.forename: E
authors.initials: E
authors.lastname: Serbinova
authors.forename: H J
authors.initials: HJ
authors.lastname: Tritschler
authors.forename: L
authors.initials: L
authors.lastname: Packer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000378:metabolism; D019328:Buthionine Sulfoximine; D002386:Cataract / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000172:deficiency / Q000378:metabolism; D019803:Glutathione Disulfide; D007908:Lens, Crystalline / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000737:chemistry / Q000494:pharmacology*; D014810:Vitamin E / Q000378:metabolism
chemical_list: D014810:Vitamin E; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008063:Thioctic Acid; D005978:Glutathione; D001205:Ascorbic Acid; D019803:Glutathione Disulfide