Galactosemia produces ARI-preventable nodal changes similar to those of diabetic neuropathy.
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.
Kamijo
M
M
Department of Pathology, University of Michigan Medical Center, Ann Arbor 48109.
Basso
M
M
Cherian
P V
PV
Hohman
T C
TC
Sima
A A
AA
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
C091470:WAY 121-509; D004376:Galactitol; D005632:Fructose; D007294:Inositol; D013012:Sorbitol; D000449:Aldehyde Reductase; D005690:Galactose