山梨医科大学雑誌　第3巻2号　047-056(1988)

Effects of Anti-Inflammatory Drugs and ONO-2235 on
Lens Aldose Reductase and on Sorbitol Accumulation
in Red Blood Cells

Kaoru AIDA, Masato TAWATA, Hideo SHINDO, Shigeo TSUKAHARA
and Toshimasa ONAYA

Abstract: Anti-inflammatory drugs and ONO-2235 were tested for their ability to inhibit lens aldose reductase and sorbitol accumulation in red blood cells. Sulindac, an anti-inflammatory drug, and ONO-2235 were shown to be potent inhibitors of aldose reductases from human cataractous lenses, bovine lenses and rat lenses. ONO-2235 was the most potent inhibitor with IC50 of 2×10^-8 M, using human lens aldose reductase. Sulindac and ONO-2235 also inhibited the accumulation of sorbitol in human red blood cells. The IC50s were 6.2×10^-6 M, and 6×10^-6 M, respectively.
Similarly, indomethacin and its prodrug, acemetacine, inhibited both aldose reductase in rat lens and sorbitol accumulation in human red blood cells. Furthermore, in diabetic rats, sulindac significantly suppressed sorbitol accumulation in red blood cells and sciatic nerves. These results suggest that sulindac as well as ONO-2235 can be useful in preventing chronic diabetic complications.

Key words: Anti-inflammatory drug, ONO-2235, Aldose reductase, sorbitol, Diabetes mellitus




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