Effect of alpha-tocopherol deficiency on indices of oxidative stress in normal and diabetic peripheral nerve.
We tested the hypothesis that oxidative stress can cause neuropathy by evaluating the effect of alpha-tocopherol depletion in normal and streptozotocin (STZ) diabetic peripheral nerve (known to be subject to oxidative stress). The end points were nerve electrophysiology and indices of oxidative stress. Studies were done on 6 groups of rats at 1 and 3 months: (1) Controls, normal alpha-tocopherol (Con[N]). (2) Controls, alpha-tocopherol-deficient (Con[-]) (3) Controls, alpha-tocopherol supplemented (Con[+]); (4) Diabetic, normal alpha-tocopherol (STZ[N]); (5) Diabetic, alpha-tocopherol-deficient (STZ[-]) (6) Diabetic, alpha-tocopherol supplemented (STZ[+]). An alpha-tocopherol-deficient diet resulted in a rapid depletion of the vitamin in plasma and sympathetic neurones (superior cervical ganglion), and a slower depletion in sensory neurones (dorsal root ganglion) and nerve. The depletion was associated with a reduction in reduced glutathione and an increase in conjugated dienes and hydroperoxides in normal rats, and resulted in similar changes, or accentuated the abnormalities, in diabetic nerves. Changes were more pronounced at 1 than 3 months and alpha-tocopherol supplementation, for the most part, did not prevent the abnormalities. alpha-Tocopherol depletion induced or worsened nerve conduction abnormalities in both sciatic-tibial and caudal nerves. Sensory fibers were more affected than motor fibers and the changes were more pronounced at 3 than 1 month. These findings support the notion that oxidative stress may cause neuropathy and that it might be mechanistically implicated in experimental diabetic neuropathy (STZ-EDN).
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905.
K K
KK
Nickander
J D
JD
Schmelzer
D A
DA
Rohwer
P A
PA
Low
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003929:Diabetic Neuropathies / Q000150:complications / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000032:analysis; D006861:Hydrogen Peroxide / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008833:Microcirculation; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000032:analysis; D018384:Oxidative Stress; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D013311:Streptozocin; D017783:Superior Cervical Ganglion / Q000378:metabolism / Q000473:pathology; D014810:Vitamin E / Q000008:administration & dosage / Q000502:physiology* / Q000627:therapeutic use; D014811:Vitamin E Deficiency / Q000150:complications* / Q000188:drug therapy
D014810:Vitamin E; D013311:Streptozocin; D006861:Hydrogen Peroxide; D005978:Glutathione; D009638:Norepinephrine