Glutathione and alpha-lipoate in diabetic rats: nerve function, blood flow and oxidative state.
BACKGROUND
Increased oxidative stress is considered to be a causal factor in the development of diabetic complications, among which peripheral neuropathy. The pathophysiology of nerve dysfunction in diabetes has been explained both by reduced endoneurial microcirculation and alterations in endoneurial metabolism. It is unclear whether antioxidants primarily improve nerve blood flow or normalise systemic or endoneurial oxidative metabolism. Therefore, we evaluated the effects of the antioxidants glutathione and alpha-lipoic acid on both nerve microcirculation and the antioxidative capacity and lipid peroxidation in experimentally diabetic rats.


METHODS
Streptozotocin-diabetic rats were treated with different doses of alpha-lipoic acid, reduced glutathione or placebo, and were compared with nondiabetic controls. We measured systemic and endoneurial antioxidants, malondialdehyde and whole blood hydrogen peroxide. Furthermore, we evaluated sciatic and tibial motor and sensory nerve conduction velocity, caudal nerve conduction velocity, and assessed sciatic nerve blood flow and vascular resistance by Laser-Doppler flowmetry.


RESULTS
We observed a rise in erythrocyte glutathione by 27 % (P < 0.05), and a trend towards decreased plasma malondialdehyde in alpha-lipoic acid, but not in glutathione-treated animals in comparison with the placebo group. Simultaneously, sciatic nerve blood flow and vascular resistance were improved by daily alpha-lipoic acid administration by 38% (P < 0.05). Peripheral nerve conduction velocity and endoneurial glutathione were not significantly influenced by antioxidant treatment.


CONCLUSIONS
Only minor beneficial effects of alpha-lipoic acid on nerve blood flow and oxidative state occur at the given doses; these effects were insufficient to improve nerve conduction deficits.
van Dam
P S
PS
University Medical Center, Utrecht, The Netherlands. P.S.vanDam@digd.azu.nl
van Asbeck
B S
BS
Van Oirschot
J F
JF
Biessels
G J
GJ
Hamers
F P
FP
Marx
J J
JJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001783:Blood Flow Velocity / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D005978:Glutathione / Q000008:administration & dosage / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010525:Peripheral Nerves / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000098:blood supply; D008063:Thioctic Acid / Q000008:administration & dosage / Q000378:metabolism*; D013979:Tibial Nerve / Q000098:blood supply; D014655:Vascular Resistance / Q000187:drug effects
D000975:Antioxidants; D008063:Thioctic Acid; D005978:Glutathione