n-acetylcarnosine and 1-1-diphenyl-2-picrylhydrazyl

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.

Topics: alpha-Crystallins; Animals; Biphenyl Compounds; Carnosine; Cataract; Cells, Cultured; Chick Embryo; Cyclic N-Oxides; Diamide; Dihydroxyphenylalanine; Disease Progression; Dose-Response Relationship, Drug; Free Radical Scavengers; Galactose; Glucocorticoids; Glutathione; Insecta; Lens, Crystalline; Lipid Peroxidation; Male; Oxidative Stress; Picrates; Protein Carbonylation; Rats; Rats, Sprague-Dawley; Spin Labels; Superoxides