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Effects of a new aldose reductase inhibitor, (2S, 4S)-6-fluoro-2′,5′-dioxospiro[chroman-4,4′-imidazolidine]-2-carboxamide (SNK-860), on the slowing of motor nerve conduction velocity and metabolic abnormalities in the peripheral nerve in acute streptozotocin-induced diabetic rats

1992; Elsevier BV; Volume: 41; Issue: 10 Linguagem: Inglês

10.1016/0026-0495(92)90289-m

1532-8600

Kuniharu Mizuno, Noriaki Kato, Akira Matsubara, Kazumasa Nakano, Masayasu Kurono,

Pain Mechanisms and Treatments

The effects of a new aldose reductase inhibitor (ARI), (2S,4S)-6-fluoro-2′,5′-dioxospiro[chroman-4,4′-imidazolidine]-2-carboxamide (SNK-860), on the slowing of motor nerve conduction velocity (MNCV) and metabolic abnormalities in sciatic nerve were investigated in acute streptozotocin (STZ)-induced diabetic rats. MNCV in the diabetic rats was significantly slower 2 weeks after STZ injection. In the following 2 weeks, treatment with SNK-860 improved MNCV in a dose-dependent manner. The efficacy of 1 mg/kg SNK-860 was equipotent to that of 20 mg/kg sorbinil. Four weeks after STZ injection, increases in sorbitol levels, decreases in myo-inositol levels, and reductions in Na+, K+-adenosine triphosphatase (ATPase) activity were observed in sciatic nerves of diabetic rats. Administration of SNK-860 for 14 days beginning 2 weeks after the induction of diabetes inhibited these metabolic abnormalities in a dose-dependent manner. SNK-860 restored all of these parameters to normal levels at a dose of 2 mg/kg. In addition, close correlations were observed between MNCV and sorbitol levels (r = −.95) and between MNCV and myo-inositol levels (r = .93) in the sciatic nerve; a close correlation was also observed between sorbitol and myo-inositol levels in the sciatic nerve (r = −.86). Therefore, it is suggested that the effect of SNK-860 on the slowing of MNCV results from normalizing the above-mentioned metabolic abnormalities in the sciatic nerve of diabetics. Thus, SNK-860 may be useful in the treatment of diabetic neuropathy.