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
[31]  
Meister A, 1989, GLUTATHIONE CHEM BIO, P367
[32]   MODELING CORTICAL CATARACTOGENESIS .13. EARLY EFFECTS ON LENS ATP ADP AND GLUTATHIONE IN THE STREPTOZOTOCIN RAT MODEL OF THE DIABETIC CATARACT [J].
MITTON, KP ;
DEAN, PAW ;
DZIALOSZYNSKI, T ;
XIONG, H ;
SANFORD, SE ;
TREVITHICK, JR .
EXPERIMENTAL EYE RESEARCH, 1993, 56 (02) :187-198
[33]   GLUTATHIONE DEFICIENCY DECREASES TISSUE ASCORBATE LEVELS IN NEWBORN RATS - ASCORBATE SPARES GLUTATHIONE AND PROTECTS [J].
MRTENSSON, J ;
MEISTER, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) :4656-4660
[34]   LIPOIC ACID AND DIABETES - EFFECT OF DIHYDROLIPOIC ACID ADMINISTRATION IN DIABETIC RATS AND RABBITS [J].
NATRAJ, CV ;
GANDHI, VM ;
MENON, KKG .
JOURNAL OF BIOSCIENCES, 1984, 6 (01) :37-46
[35]   NUCLEAR CATARACT AND MYOPIA DURING HYPERBARIC-OXYGEN THERAPY [J].
PALMQUIST, BM ;
PHILIPSON, B ;
BARR, PO .
BRITISH JOURNAL OF OPHTHALMOLOGY, 1984, 68 (02) :113-117
[36]   HEPATIC LIPOATE UPTAKE [J].
PEINADO, J ;
SIES, H ;
AKERBOOM, TPM .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1989, 273 (02) :389-395
[37]   ANTIOXIDANT ACTIVITY OF DIHYDROLIPOATE AGAINST MICROSOMAL LIPID-PEROXIDATION AND ITS DEPENDENCE ON ALPHA-TOCOPHEROL [J].
SCHOLICH, H ;
MURPHY, ME ;
SIES, H .
BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 1001 (03) :256-261
[38]   ESTIMATION OF TOTAL PROTEIN-BOUND AND NONPROTEIN SULFHYDRYL GROUPS IN TISSUE WITH ELLMANS REAGENT [J].
SEDLAK, J ;
LINDSAY, RH .
ANALYTICAL BIOCHEMISTRY, 1968, 25 (1-3) :192-&
[39]   THIOCTIC ACID PROTECTS AGAINST ISCHEMIA-REPERFUSION INJURY IN THE ISOLATED PERFUSED LANGENDORFF HEART [J].
SERBINOVA, E ;
REZNICK, SKAZ ;
PACKER, L .
FREE RADICAL RESEARCH COMMUNICATIONS, 1992, 17 (01) :49-58
[40]  
SPECTOR A, 1984, CIBA F SYMP, V106, P48