5-S-GAD, a novel radical scavenging compound, prevents lens opacity development.
The ability of N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD)-a novel catechol derivative isolated from an insect as an antibacterial substance-to scavenge free radicals and prevent cataract progression was examined. 5-S-GAD scavenged 1,1-diphenylpicrylhydrazyl (DPPH) and superoxide anions (O(2)(*)(-)), and inhibited lipid peroxidation. It also significantly inhibited the onset of glucocorticoid-induced lens opacification in chick embryos. These effects of 5-S-GAD were stronger than those of N-acetylcarnosine and TEMPOL, which are reported to be effective radical scavengers in the prevention of cataract progression. 5-S-GAD clearly delayed the maturation of cataracts induced by diamide in cultured lenses of rats. Daily instillation of 5-S-GAD retarded the development of lens opacity in galactose-fed rats. Biochemical analysis of the lenses revealed that 20-kDa proteins, presumably consisting of alpha-crystallin, were the most susceptible to oxidative stress, which leads to the carbonylation of the side chains of these proteins. alpha-Crystallin carbonylation induced by diamide or galactose was notably inhibited by 5-S-GAD in a dose-dependent manner. Our results show that 5-S-GAD prevents acute lens opacification in these short-term experimental models, possibly in part by virtue of its antioxidative property, and 5-S-GAD is expected to have long-term pharmaceutical effects.
Akiyama
Nobuko
N
Natori Laboratory, RIKEN, Wako-shi, Saitama, Japan. fnobuko@riken.jp
Umeda
Izumi O
IO
Sogo
Shunji
S
Nishigori
Hideo
H
Tsujimoto
Masafumi
M
Natori
Shunji
S
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism; D002336:Carnosine / Q000031:analogs & derivatives / Q000494:pharmacology; D002386:Cataract / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D002642:Chick Embryo; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003958:Diamide / Q000633:toxicity; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005690:Galactose / Q000008:administration & dosage / Q000633:toxicity; D005938:Glucocorticoids / Q000008:administration & dosage / Q000633:toxicity; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D007313:Insecta; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010851:Picrates / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism; D038201:alpha-Crystallins / Q000378:metabolism*
D001713:Biphenyl Compounds; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005938:Glucocorticoids; C100496:N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine; D010851:Picrates; D013113:Spin Labels; D038201:alpha-Crystallins; C033681:N-acetylcarnosine; D003958:Diamide; D013481:Superoxides; D004295:Dihydroxyphenylalanine; D002336:Carnosine; C004931:1,1-diphenyl-2-picrylhydrazyl; D005978:Glutathione; C001803:tempol; D005690:Galactose