A lipoic acid-gamma linolenic acid conjugate is effective against multiple indices of experimental diabetic neuropathy.
Untreated streptozotocin-diabetic (7 weeks duration) rats showed reductions (all p < 0.01; percentages in brackets) in motor and sensory nerve conduction velocity (MNCV; 14%, SNCV; 17%) and in sciatic nerve contents of nerve growth factor (NGF; 57%), substance P (SP; 53%) and neuropeptide Y (NPY; 39%). Treatment with a gamma-linolenic acid-alpha-lipoic acid conjugate (GLA-LA; 35 mg x day(-1) x rat(-1)) attenuated (p < 0.05) these reductions to MNCV (8%), SNCV (5%), NGF (19%), SP (23%), NPY (20%), such that the values in GLA-LA-treated diabetic rats did not differ significantly from those of control non-diabetic animals. Treatment with alpha-lipoic acid alone at 100 mg/kg i.p. was without effect on these variables except for NGF (33% reduction, p < 0.05) and treatment with the antioxidant, butylated hydroxytoluene (1.5% dietary supplement) did not affect any deficits. These data show that GLA-LA is effective in improving both electrophysiological and neurochemical correlates of experimental diabetic neuropathy.
Department of Pharmacology, Queen Mary and Westfield College, London, UK.
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L
Hounsom
D F
DF
Horrobin
H
H
Tritschler
R
R
Corder
D R
DR
Tomlinson
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013373:Substance P / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D000975:Antioxidants; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D002084:Butylated Hydroxytoluene; D013373:Substance P; D008063:Thioctic Acid; D017965:gamma-Linolenic Acid