title: Galactosemia produces ARI-preventable nodal changes similar to those of diabetic neuropathy.
abstract: The present study was designed to examine the development of structural changes, characteristic of diabetic neuropathy, in chronic galactosemia and their responsiveness to inhibition of the polyol-pathway. Sprague-Dawley rats weighing 70-90 g were given a 50% galactose diet continued for 4 or 8 months. Half of these animals were simultaneously given the aldose reductase inhibitor (ARI) WAY 121-509. ARI-treatment normalized galactitol and myoinositol levels in the sciatic nerve. At 4 months, sciatic nerve conduction velocity (NCV) in galactosemic rats was reduced by 30% which was prevented in ARI-treated rats. At 8 months galactosemia reduced NCV to 58% of control values, while ARI-treatment for 8 months improved NCV to 71% of control values. ARI-treatment prevented in galactosemic rats nodal structural changes characteristic of diabetic neuropathy, whereas axonal atrophy was not affected by ARI-treatment, which may in part account for the only partial prevention of the NCV slowing at 8 months. Nerve fiber regeneration was increased 4-fold in ARI-treated rats compared with untreated galactosemic rats. These data suggest that chronic galactosemia produces a neuropathy structurally similar to diabetic neuropathy. The lack of an ARI-treatment effect on axonal atrophy suggests that this defect is not polyol related in galactosemia.
authors: Department of Pathology, University of Michigan Medical Center, Ann Arbor 48109.
authors: M
authors: M
authors: Kamijo
authors: M
authors: M
authors: Basso
authors: P V
authors: PV
authors: Cherian
authors: T C
authors: TC
authors: Hohman
authors: A A
authors: AA
authors: Sima
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001835:Body Weight / Q000187:drug effects; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005632:Fructose / Q000378:metabolism; D004376:Galactitol / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005693:Galactosemias / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D007294:Inositol / Q000378:metabolism; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013012:Sorbitol / Q000378:metabolism; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology
chemical_list: C091470:WAY 121-509; D004376:Galactitol; D005632:Fructose; D007294:Inositol; D013012:Sorbitol; D000449:Aldehyde Reductase; D005690:Galactose