Improvement Of Peripheral Nerve Structure By 15‐Month Aldose Reductase Inhibition With Fidarestat In Stz‐Induced Diabetic Rats

<jats:p>There has been no report documenting the effects of long‐term aldose reductase (AR) inhibition one year or more on peripheral neuropathy of streptozotocin‐induced diabetic rats (STZ‐rats). Fidarestat (SNK‐860) is a potent AR inhibitor that possesses the beneficial effects on the nerve dysfunction in early stage of diabetic rats (1). In the present study, we investigated the effects of 15 months of treatment with fidarestat on functional, morphological and metabolic abnormalities in the peripheral nerve of STZ‐rats. Fidarestat treatment inhibited the slowing of F‐wave conduction velocity and motor nerve conduction velocity by about 70% and normalized the slowing of sensory nerve conduction velocity. Morphometric analysis of myelinated fibers demonstrated that the frequencies of abnormal fibers such as paranodal demyelination, Wallerian degeneration and axonal sequestration were reduced to the extent of normal levels by fidarestat. Axonal atrophy, reduction of myelin sheath thickness and ratio of large fibers were also inhibited. The effects of fidarestat on functional and morphological changes were accompanied by correction of the increased sorbitol, fructose and decreased <jats:italic>myo</jats:italic>‐inositol in nerve. It was thus demonstrated that long‐term inhibition of increased polyol pathway flux by fidarestat was beneficial for the development of functional and structural neuropathy in STZ‐rats.</jats:p><jats:p>(1) Mizuno, K., et al. (1999). J. Diab. Comp., 13,141‐150.</jats:p>