EFFECT OF LONG-TERM TREATMENT WITH A NEW ALDOSE REDUCTASE INHIBITOR, XOSPIRO-[CHROMAN-4,4'-IMIDAZOLIDINE]-2-CARBOXAMIDE (SNK-860), ON PERIPHERAL NEUROPATHY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

We studied the long-term effects of a new aldose reductase inhibitor, oxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (SNK-860), on funct ional, biochemical, and structural changes in peripheral nerve of stre ptozotocin (STZ)-induced diabetic rats. During the experimental period of 26 weeks, the delayed motor-nerve conduction in diabetic rats was significantly prevented by SNK-860 treatment, and elevated sorbitol le vels and reduced myo-inositol levels were normalized to 100% and 71% o f control levels, respectively. Teased nerve fiber studies demonstrate d that the frequency of abnormal fibers was significantly reduced in t reated diabetic rats. Morphometric analysis of myelinated fibers also disclosed prevention of axonal atrophy, distorted axonal circularity a nd preservation of large-sized fibers following SNK-860 treatment. The se results suggest that long-term treatment with SNK-860 has a benefic ial preventive effect on the development of experimental diabetic neur opathy.