title: Cataract formation through the polyol pathway is associated with free radical production.
abstract: The relationship between sugar cataract formation and radical production was investigated. The in vivo formation of free radicals in the lenses of rats fed on a diet containing 25% and 50% galactose was studied using the electron spin resonance (ESR) spin trapping method. Effects of treatment with aldose reductase inhibitor (ARI) SNK-860 on free radical formation were determined in 25% and 50% galactose fed rats. Hydroxyl radical (*OH) adduct of the spin trap 5,5'-dimethyl-1-pyrroline- N -oxide (DMPO) was directly detected in the superficial cortical cataract obtained from 25% and 50% galactose-fed rats. *OH production was completely inhibited by ARI SNK-860 in both galactose groups. Polyol accumulated in rat lenses given 50% galactose with a peak within the first 2 weeks, and was significantly inhibited by SNK-860. The increase in *OH production was considered with the polyol accumulation in both galactose groups. The dose of SNK-860 to inhibit *OH by 50% level was estimated at 3 m by the method of kinetic competition in vitro experiment. SNK-860 is not an effective *OH scavenger compared to other *OH scavengers. The results of the present study suggest that *OH is indirectly inhibited by SNK-860 resulting from decreasing polyol and *OH formation is related to sugar cataract formation in early stages, possibly via the Fenton reaction involving H2O2 produced from the activated polyol pathway. We suppose that *OH may accelerate damage to the cell membrane of lens fibers resulting from polyol accumulation *OH may play an important role in the early stage of sugar cataract process.
authors: Department of Ophthalmology, Fukui Medical University, Fukui, Japan.
authors: E
authors: E
authors: Kubo
authors: N
authors: N
authors: Miyoshi
authors: M
authors: M
authors: Fukuda
authors: Y
authors: Y
authors: Akagi
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D002386:Cataract / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005690:Galactose / Q000009:adverse effects*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007093:Imidazoles / Q000627:therapeutic use; D048289:Imidazolidines; D008297:Male; D008954:Models, Biological; D011108:Polymers / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D011108:Polymers; C024617:polyol; D017665:Hydroxyl Radical; C077139:fidarestat; D000449:Aldehyde Reductase; D005690:Galactose