Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy.
OBJECTIVE
To determine whether lipoic acid (LA) will reduce oxidative stress in diabetic peripheral nerves and improve neuropathy.


METHODS
We used the model of streptozotocin-induced diabetic neuropathy (SDN) and evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF), electrophysiology, and indexes of oxidative stress in peripheral nerves affected by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA, in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times per week after onset of diabetes.


RESULTS
NBF in SDN was reduced by 50%; LA did not affect the NBF of normal nerves but improved that of SDN in a dose-dependent manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited normal NBF. The most sensitive and reliable indicator of oxidative stress was reduction in reduced glutathione, which was significantly reduced in streptozotocin-induced diabetic and alpha-tocopherol-deficient nerves; it was improved in a dose-dependent manner in LA-supplemented rats. The conduction velocity of the digital nerve was reduced in SDN and was significantly improved by LA.


CONCLUSIONS
These studies suggest that LA improves SDN, in significant part by reducing the effects of oxidative stress. The drug may have potential in the treatment of human diabetic neuropathy.
Nagamatsu
M
M
Department of Neurology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Nickander
K K
KK
Schmelzer
J D
JD
Raya
A
A
Wittrock
D A
DA
Tritschler
H
H
Low
P A
PA
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009431:Neural Conduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D008063:Thioctic Acid / Q000494:pharmacology*; D013997:Time Factors; D014802:Vitamin A Deficiency / Q000503:physiopathology; D014810:Vitamin E / Q000378:metabolism; D015431:Weight Loss
D014810:Vitamin E; D008063:Thioctic Acid; D005978:Glutathione