Cataract formation through the polyol pathway is associated with free radical production.
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.
Kubo
E
E
Department of Ophthalmology, Fukui Medical University, Fukui, Japan.
Miyoshi
N
N
Fukuda
M
M
Akagi
Y
Y
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
D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D011108:Polymers; C024617:polyol; D017665:Hydroxyl Radical; C077139:fidarestat; D000449:Aldehyde Reductase; D005690:Galactose