Therapeutic Effects of Aldose Reductase Inhibitor on Experimental Diabetic Neuropathy through Synthesis/Secretion of Nerve Growth Factor

• Published in: Experimental neurology 1998-06, Vol.151 (2), p.215-220
• Main Authors: Ohi, Takekazu, Saita, Kazuko, Furukawa, Shoei, Ohta, Mitsuhiro, Hayashi, Kyozo, Matsukura, Shigeru
• Format: Article
• Language: English
• Subjects: Aldehyde Reductase - antagonists & inhibitors; aldose reductase inhibitor; Animals; Associated diseases and complications; Biological and medical sciences; Catechols - pharmacology; Cells, Cultured; Ciliary Neurotrophic Factor; CNTF; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - metabolism; diabetic neuropathy; Electrophysiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Inhibitors - pharmacology; Male; Medical sciences; Nerve Growth Factors - biosynthesis; Nerve Growth Factors - secretion; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - secretion; Neuroprotective Agents - pharmacology; NGF; Rats; Rats, Sprague-Dawley; Rhodanine - analogs & derivatives; Rhodanine - pharmacology; Schwann cell culture; Schwann Cells - cytology; Schwann Cells - drug effects; Schwann Cells - enzymology; Sciatic Nerve - chemistry; Sciatic Nerve - cytology; Sciatic Nerve - physiology; Thiazolidines
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1998.6821

We investigated alterations in nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) contents during treatment with epalrestat, an aldose reductase inhibitor (ARI), on streptozotocin (STZ)-induced diabetic neuropathy in rats. Diabetic rats showed a statistically significant reduction in H-wave-related sensory nerve conduction velocity (HSNCV) and in NGF content in sciatic nerves during the experiment of 8 weeks. No reduction in the CNTF content in sciatic nerves was seen in the diabetic rats. The epalrestat treatment, which started 4 weeks after STZ injection, resulted in a significantly greater NGF content and faster HSNCV than those in untreated diabetic rats. But no statistically significant alterations of motor nerve conduction velocity (MNCV) or CNTF content were seen during the treatment. ARI showed the stimulating effect for NGF synthesis/secretion in rat Schwann cell culturein vitro.These findings suggest that decreased levels of NGF in diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy in these rats and further show that epalrestat treatment can be useful for the treatment of diabetic neuropathy through NGF-induction in Schwann cells and/or inhibition of the polyol pathway.