Stereospecific Effects of R-Lipoic Acid on Buthionine Sulfoximine-Induced Cataract Formation in Newborn Rats

• Published in: Biochemical and biophysical research communications Vol. 221; no. 2; pp. 422 - 429
• Main Authors: Maitra, Indrani, Serbinova, Elena, Tritschler, Hans J., Packer, Lester
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.04.1996
• Subjects: Animals; Animals, Newborn; Ascorbic Acid - metabolism; Buthionine Sulfoximine; Cataract - chemically induced; Cataract - prevention & control; Female; Glutathione - analogs & derivatives; Glutathione - deficiency; Glutathione - metabolism; Glutathione Disulfide; Lens, Crystalline - metabolism; Methionine Sulfoximine - analogs & derivatives; Methionine Sulfoximine - toxicity; Pregnancy; Rats; Rats, Sprague-Dawley; Stereoisomerism; Thioctic Acid - chemistry; Thioctic Acid - pharmacology; Vitamin E - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1996.0611

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 α-lipoate. R- and racemic α-lipoate decreased cataract formation from 100% (buthionine sulfoximine only) to 55% (buthionine sulfoximine + R-α-lipoic acid) and 40% (buthionine sulfoximine + rac-α-lipoic acid) (p < 0.05 compared to buthionine sulfoximine only). S-α-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-α-lipoic acid or rac-α-lipoic acid were administered with buthionine sulfoximine; S-α-lipoic acid administration had no protective effect on lens antioxidants. When enantiomers of α-lipoic acid were administered to animals, R-α-lipoc acid was taken up by lens and reached concentrations 2- to 7-fold greater than those of S-α-lipoic acid, with rac-α-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-α-lipoic acid-treated animals and the lowest levels in S-α-lipoic acid-treated animals. These results indicate that the protective effects of α-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-α-lipoic acid by lens cells.