<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>In the present study, the authors examined whether treating
streptozotocin-induced diabetic rats with the combination
of <italic>α</italic>-lipoic acid and fidarestat, an aldose reductase inhibitor,
can promote the formation of dihydrolipoic acid
in diabetic animals and thereby enhance the efficacy of
<italic>α</italic>-lipoic acid as monotherapy toward preventing diabetic
vascular and neural dysfunction.Treating diabetic rats with
the combination of 0.25% <italic>α</italic>-lipoic acid (in the diet) and
fidarestat (3 mg/kg body weight) prevented the diabetesinduced
slowing of motor nerve conduction velocity and
endoneurial blood flow. This therapy also significantly improved
acetylcholine-mediated vasodilation in epineurial
arterioles of the sciatic nerve compared to nontreated diabetic
rats. Treating diabetic rats with 0.25% <italic>α</italic>-lipoic acid
and fidarestat (3 mg/kg body weight) was equally or more
effective in preventing vascular and neural dysfunction than
was monotherapy of diabetic rats with higher doses of
<italic>α</italic>-lipoic acid or fidarestat. Treating diabetic rats with the
combination of 0.25% <italic>α</italic>-lipoic acid and fidarestat (3 mg/kg
body weight) significantly improved several markers of oxidative
stress and increased the serum levels of both <italic>α</italic>-lipoic
acid and dihydrolipoic acid. These studies suggest that combination
therapy consisting of <italic>α</italic>-lipoic acid and fidarestat
may be more efficacious in preventing diabetes-induced vascular
and neural dysfunction in peripheral tissue compared
to monotherapy, which requires higher doses to be equally effective. The effect of this combination therapy may in part
be due to the increased production and/or level of dihydrolipoic
acid.</p>
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Exp Diabesity Res. 2004; 5(2):123-135