Cataract formation through the polyol pathway is associated with free radical production

The relationship between sugar cataract formation and radical production wa s investigated. The in vivo formation of free radicals in the lenses of rat s fed on a diet containing 25% and 50% galactose was studied using the elec tron spin resonance (ESR) spin trapping method. Effects of treatment with a ldose reductase inhibitor (ARI) SNK-860 on Gee radical formation were deter mined 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 detecte d 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-86 0. The increase in . OH production was considered with the polyol accumulat ion in both galactose groups. The dose of SNK-860 to inhibit . OH by 50% le vel was estimated at 3 M by the method of kinetic competition in vitro expe riment. SNK-860 is not an effective . OH scavenger compared to other . OH s cavengers. The results of the present study suggest that . OH is indirectly inhibited by SNK-860 resulting from decreasing polyol and . OH formation i s related to sugar cataract formation in early stages, possibly via the Fen ton 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 e arly stage of sugar cataract process. (C) 1999 Academic Press.