ALPHA-LIPOIC ACID PREVENTS BUTHIONINE SULFOXIMINE-INDUCED CATARACT FORMATION IN NEWBORN RATS

被引:69
作者
MAITRA, I
SERBINOVA, E
TRISCHLER, H
PACKER, L
机构
[1] UNIV CALIF BERKELEY, DEPT MOLEC & CELL BIOL, BERKELEY, CA 94720 USA
[2] ASTA MED, FRANKFURT, GERMANY
关键词
LIPOIC ACID; CATARACT; NEWBORN ANIMALS; L-BUTHIONINE(S; R)-SULFOXIMINE; GLUTATHIONE; VITAMIN-E; ASCORBIC ACID; FREE RADICALS;
D O I
10.1016/0891-5849(94)00195-P
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:823 / 829
页数:7
相关论文
共 44 条
[1]  
Aebi H., 1974, METHODS ENZYMATIC AN, P673, DOI [10.1016/B978-0-12-091302-2.50032-3, DOI 10.1016/B978-0-12-091302-2.50032-3]
[2]  
ANDERSON ME, 1985, METHOD ENZYMOL, V113, P548
[3]   ASCORBATE FREE-RADICAL REDUCTASE, A KEY ENZYME OF THE ASCORBIC-ACID SYSTEM [J].
ARRIGONI, O ;
DIPIERRO, S ;
BORRACCINO, G .
FEBS LETTERS, 1981, 125 (02) :242-244
[4]  
BANDO M, 1988, JPN J OPHTHALMOL, V32, P176
[5]   ACTIVITIES OF ASCORBATE FREE-RADICAL REDUCTASE AND H2O2-DEPENDENT NADH OXIDATION IN SENILE CATARACTOUS HUMAN LENSES [J].
BANDO, M ;
OBAZAWA, H .
EXPERIMENTAL EYE RESEARCH, 1990, 50 (06) :779-784
[6]   ROLE OF FREE-RADICALS IN CANCER AND ATHEROSCLEROSIS [J].
BANKSON, DD ;
KESTIN, M ;
RIFAI, N .
CLINICS IN LABORATORY MEDICINE, 1993, 13 (02) :463-480
[7]  
Bergmeyer HU, 1974, METHOD ENZYMAT AN, V1, P465
[8]   MOLECULAR MECHANISM OF CATARACTOGENESIS .3. TOXIC METABOLITES OF OXYGEN AS INITIATORS OF LIPID-PEROXIDATION AND CATARACT [J].
BHUYAN, KC ;
BHUYAN, DK .
CURRENT EYE RESEARCH, 1984, 3 (01) :67-81
[9]   SUPEROXIDE-DISMUTASE OF EYE - RELATIVE FUNCTIONS OF SUPEROXIDE-DISMUTASE AND CATALASE IN PROTECTING OCULAR LENS FROM OXIDATIVE DAMAGE [J].
BHUYAN, KC ;
BHUYAN, DK .
BIOCHIMICA ET BIOPHYSICA ACTA, 1978, 542 (01) :28-38
[10]   NEAR-TOTAL GLUTATHIONE DEPLETION AND AGE-SPECIFIC CATARACTS INDUCED BY BUTHIONINE SULFOXIMINE IN MICE [J].
CALVIN, HI ;
MEDVEDOVSKY, C ;
WORGUL, BV .
SCIENCE, 1986, 233 (4763) :553-555