M. Kamijo et al., GALACTOSEMIA PRODUCES ARI-PREVENTABLE NODAL CHANGES SIMILAR TO THOSE OF DIABETIC NEUROPATHY, Diabetes research and clinical practice, 25(2), 1994, pp. 117-129
The present study was designed to examine the development of structura
l changes, characteristic of diabetic neuropathy, in chronic galactose
mia and their responsiveness to inhibition of the polyol-pathway. Spra
gue-Dawley rats weighing 70-90 g were given a 50% galactose diet conti
nued for 4 or 8 months. Half of these animals were simultaneously give
n the aldose reductase inhibitor (ARI) WAY 121-509. ARI-treatment norm
alized galactitol and myoinositol levels in the sciatic nerve. At 4 mo
nths, sciatic nerve conduction velocity (NCV) in galactosemic rats was
reduced by 30% which was prevented in ARI-treated rats. At 8 months g
alactosemia reduced NCV to 58% of control values, while ARI-treatment
for 8 months improved NCV to 71% of control values. ARI-treatment prev
ented in galactosemic rats nodal structural changes characteristic of
diabetic neuropathy, whereas axonal atrophy was not affected by ARI-tr
eatment, 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. Th
ese data suggest that chronic galactosemia produces a neuropathy struc
turally similar to diabetic neuropathy. The lack of an ARI-treatment e
ffect on axonal atrophy suggests that this defect is not polyol relate
d in galactosemia.