Effects of long-term aldose reductase inhibition on development of experimental diabetic neuropathy. Ultrastructural and morphometric studies of sural nerve in streptozocin-induced diabetic rats. 1990

S Yagihashi, and M Kamijo, and Y Ido, and D J Mirrlees
Department of Pathology, Hirosaki University School of Medicine, Japan.

There is controversy over the efficacy of aldose reductase inhibitors in preventing the development of peripheral nerve lesions in experimental diabetes. This study was designed to show whether long-term (28-wk) inhibition of aldose reductase by ponalrestat influences structural changes in peripheral sensory nerve in rats with chronic streptozocin-induced diabetes. Sciatic nerve levels of sorbitol and fructose were significantly reduced but not completely normalized by ponalrestat treatment. myo-Inositol levels, which tended to decrease in diabetic rats, were significantly increased by ponalrestat treatment and exceeded the level in nondiabetic control rats (P less than 0.01). Ponalrestat treatment significantly increased nerve conduction velocity over the 28 wk of treatment (P less than 0.05), but levels remained well below those of control rats. Structural analysis of sural nerve of diabetic rats disclosed significant preventive effects of ponalrestat on the reduction in myelinated nerve fiber size and fiber occupancy. Axon-fiber size ratio was also preserved in the ponalrestat-treated group. However, diffuse deposition of glycogen and increased glycogenosomes within axons were not influenced by ponalrestat treatment. In contrast to the effect on myelinated nerve fibers, morphometry of unmyelinated nerve fibers did not reveal a significant effect of ponalrestat treatment. These results suggest that chronic treatment with an aldose reductase inhibitor has beneficial effects on the peripheral sensory nerve of experimentally diabetic rats. The effects were primarily on myelinated rather than unmyelinated nerve fibers.

UI MeSH Term Description Entries
D007294 Inositol An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. Myoinositol,Chiro-Inositol,Mesoinositol,Chiro Inositol
D008297 Male Males
D009412 Nerve Fibers Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM. Cerebellar Mossy Fibers,Mossy Fibers, Cerebellar,Cerebellar Mossy Fiber,Mossy Fiber, Cerebellar,Nerve Fiber
D009413 Nerve Fibers, Myelinated A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves. A Fibers,B Fibers,Fiber, Myelinated Nerve,Fibers, Myelinated Nerve,Myelinated Nerve Fiber,Myelinated Nerve Fibers,Nerve Fiber, Myelinated
D009431 Neural Conduction The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus. Nerve Conduction,Conduction, Nerve,Conduction, Neural,Conductions, Nerve,Conductions, Neural,Nerve Conductions,Neural Conductions
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D003929 Diabetic Neuropathies Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325) Diabetic Amyotrophy,Diabetic Autonomic Neuropathy,Diabetic Neuralgia,Diabetic Polyneuropathy,Neuralgia, Diabetic,Asymmetric Diabetic Proximal Motor Neuropathy,Diabetic Asymmetric Polyneuropathy,Diabetic Mononeuropathy,Diabetic Mononeuropathy Simplex,Diabetic Neuropathy, Painful,Mononeuropathy, Diabetic,Symmetric Diabetic Proximal Motor Neuropathy,Amyotrophies, Diabetic,Amyotrophy, Diabetic,Asymmetric Polyneuropathies, Diabetic,Asymmetric Polyneuropathy, Diabetic,Autonomic Neuropathies, Diabetic,Autonomic Neuropathy, Diabetic,Diabetic Amyotrophies,Diabetic Asymmetric Polyneuropathies,Diabetic Autonomic Neuropathies,Diabetic Mononeuropathies,Diabetic Mononeuropathy Simplices,Diabetic Neuralgias,Diabetic Neuropathies, Painful,Diabetic Neuropathy,Diabetic Polyneuropathies,Mononeuropathies, Diabetic,Mononeuropathy Simplex, Diabetic,Mononeuropathy Simplices, Diabetic,Neuralgias, Diabetic,Neuropathies, Diabetic,Neuropathies, Diabetic Autonomic,Neuropathies, Painful Diabetic,Neuropathy, Diabetic,Neuropathy, Diabetic Autonomic,Neuropathy, Painful Diabetic,Painful Diabetic Neuropathies,Painful Diabetic Neuropathy,Polyneuropathies, Diabetic,Polyneuropathies, Diabetic Asymmetric,Polyneuropathy, Diabetic,Polyneuropathy, Diabetic Asymmetric,Simplex, Diabetic Mononeuropathy,Simplices, Diabetic Mononeuropathy
D000449 Aldehyde Reductase An enzyme that catalyzes reversibly the oxidation of an aldose to an alditol. It possesses broad specificity for many aldoses. EC 1.1.1.21. Aldose Reductase,Aldose Reductase Ia,Aldose Reductase Ib,Erythrose Reductase,Xylose Reductase,Reductase Ia, Aldose,Reductase Ib, Aldose,Reductase, Aldehyde,Reductase, Aldose,Reductase, Erythrose,Reductase, Xylose
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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