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Glutathione and α‐lipoate in diabetic rats: nerve function, blood flow and oxidative state
Author(s) -
Van Dam P. S.,
Van Asbeck B. S.,
Van Oirschot J. F. L. M.,
Biessels G. J.,
Hamers F. P. T.,
Marx J. J. M.
Publication year - 2001
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2001.00832.x
Subject(s) - endocrinology , medicine , sciatic nerve , nerve conduction velocity , glutathione , malondialdehyde , lipoic acid , diabetic neuropathy , microcirculation , oxidative stress , glutathione peroxidase , diabetes mellitus , chemistry , superoxide dismutase , antioxidant , biochemistry , enzyme
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 α‐lipoic acid on both nerve microcirculation and the antioxidative capacity and lipid peroxidation in experimentally diabetic rats. Materials and Methods Streptozotocin‐diabetic rats were treated with different doses of α‐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 α‐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 α‐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 α‐lipoic acid on nerve blood flow and oxidative state occur at the given doses; these effects were insufficient to improve nerve conduction deficits.