Effect of long-term treatment with a new aldose reductase inhibitor, (2S,4S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazolidine]-2-carbox amide (SNK-860), on peripheral neuropathy in streptozotocin-induced diabetic rats.
We studied the long-term effects of a new aldose reductase inhibitor, (2S,4S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazolidine]-2- carboxamide (SNK-860), on functional, biochemical, and structural changes in peripheral nerve of streptozotocin (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 levels and reduced myo-inositol levels were normalized to 100% and 71% of control levels, respectively. Teased nerve fiber studies demonstrated that the frequency of abnormal fibers was significantly reduced in treated diabetic rats. Morphometric analysis of myelinated fibers also disclosed prevention of axonal atrophy, distorted axonal circularity and preservation of large-sized fibers following SNK-860 treatment. These results suggest that long-term treatment with SNK-860 has a beneficial preventive effect on the development of experimental diabetic neuropathy.
Kato
N
N
Department of Pharmacology, Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan.
Mizuno
K
K
Matsubara
A
A
Nakano
K
K
Kurono
M
M
Yagihashi
S
S
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013012:Sorbitol / Q000378:metabolism
D007093:Imidazoles; D048289:Imidazolidines; D007294:Inositol; D013012:Sorbitol; C077139:fidarestat; D000449:Aldehyde Reductase