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.
Copyright 1999 Academic Press.