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Effects of alpha-lipoic acid on neurovascular function in diabetic rats: interaction with essential fatty acids.
Diabetologia 1998; 41(4):390-9D

Abstract

Elevated oxidative stress and impaired n-6 essential fatty acid metabolism contribute to defective nerve conduction velocity (NCV) and perfusion in diabetic rats, which may be corrected by free radical scavenger and gamma-linolenic acid (GLA) treatments. Alpha-lipoic acid (LPA) has antioxidant actions and both LPA racemate (racLPA) and GLA treatments produced benefits in clinical neuropathy trials. The aims were to study LPA action on neurovascular function in diabetic rats and to investigate potential interactions for co-treatment with GLA and other essential fatty acids. After 6 weeks of diabetes, 2 weeks of racLPA treatment corrected 20% sciatic motor and 14% saphenous sensory NCV deficits. The ED50 for motor NCV restoration was approximately 38 mg kg(-1) day(-1). racLPA also corrected a 49% diabetic deficit in sciatic endoneurial blood flow. R and S-LPA enantiomers were equipotent in correcting NCV and blood flow deficits. Treatment of diabetic rats with low doses (20 mg kg(-1) day(-1)) of racLPA and GLA, while having modest effects on their own, showed evidence of marked synergistic action in joint treatment, completely correcting motor NCV and blood flow deficits. This was also noted for the novel compound, SOC0150, which contains equimolar proportions of LPA and GLA (ED50 9.3 mg kg(-1) day(-1), containing 3.5 mg LPA). NCV effects also showed marked synergism when racLPA:GLA ratios were varied over a 1:3-3:1 range. In contrast, a compound containing LPA and the n-3 component, docosahexaenoic acid, showed similar activity to LPA alone. Thus, LPA-GLA interactions yield drug combinations and compounds with an order of magnitude increase in efficacy against experimental diabetic neuropathy and are worthy of consideration for clinical trials.

Authors+Show Affiliations

Department of Biomedical Sciences, University of Aberdeen, Scotland, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9562342

Citation

Cameron, N E., et al. "Effects of Alpha-lipoic Acid On Neurovascular Function in Diabetic Rats: Interaction With Essential Fatty Acids." Diabetologia, vol. 41, no. 4, 1998, pp. 390-9.
Cameron NE, Cotter MA, Horrobin DH, et al. Effects of alpha-lipoic acid on neurovascular function in diabetic rats: interaction with essential fatty acids. Diabetologia. 1998;41(4):390-9.
Cameron, N. E., Cotter, M. A., Horrobin, D. H., & Tritschler, H. J. (1998). Effects of alpha-lipoic acid on neurovascular function in diabetic rats: interaction with essential fatty acids. Diabetologia, 41(4), pp. 390-9.
Cameron NE, et al. Effects of Alpha-lipoic Acid On Neurovascular Function in Diabetic Rats: Interaction With Essential Fatty Acids. Diabetologia. 1998;41(4):390-9. PubMed PMID: 9562342.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of alpha-lipoic acid on neurovascular function in diabetic rats: interaction with essential fatty acids. AU - Cameron,N E, AU - Cotter,M A, AU - Horrobin,D H, AU - Tritschler,H J, PY - 1998/4/30/pubmed PY - 1998/4/30/medline PY - 1998/4/30/entrez SP - 390 EP - 9 JF - Diabetologia JO - Diabetologia VL - 41 IS - 4 N2 - Elevated oxidative stress and impaired n-6 essential fatty acid metabolism contribute to defective nerve conduction velocity (NCV) and perfusion in diabetic rats, which may be corrected by free radical scavenger and gamma-linolenic acid (GLA) treatments. Alpha-lipoic acid (LPA) has antioxidant actions and both LPA racemate (racLPA) and GLA treatments produced benefits in clinical neuropathy trials. The aims were to study LPA action on neurovascular function in diabetic rats and to investigate potential interactions for co-treatment with GLA and other essential fatty acids. After 6 weeks of diabetes, 2 weeks of racLPA treatment corrected 20% sciatic motor and 14% saphenous sensory NCV deficits. The ED50 for motor NCV restoration was approximately 38 mg kg(-1) day(-1). racLPA also corrected a 49% diabetic deficit in sciatic endoneurial blood flow. R and S-LPA enantiomers were equipotent in correcting NCV and blood flow deficits. Treatment of diabetic rats with low doses (20 mg kg(-1) day(-1)) of racLPA and GLA, while having modest effects on their own, showed evidence of marked synergistic action in joint treatment, completely correcting motor NCV and blood flow deficits. This was also noted for the novel compound, SOC0150, which contains equimolar proportions of LPA and GLA (ED50 9.3 mg kg(-1) day(-1), containing 3.5 mg LPA). NCV effects also showed marked synergism when racLPA:GLA ratios were varied over a 1:3-3:1 range. In contrast, a compound containing LPA and the n-3 component, docosahexaenoic acid, showed similar activity to LPA alone. Thus, LPA-GLA interactions yield drug combinations and compounds with an order of magnitude increase in efficacy against experimental diabetic neuropathy and are worthy of consideration for clinical trials. SN - 0012-186X UR - https://www.unboundmedicine.com/medline/citation/9562342/Effects_of_alpha_lipoic_acid_on_neurovascular_function_in_diabetic_rats:_interaction_with_essential_fatty_acids_ L2 - https://dx.doi.org/10.1007/s001250050921 DB - PRIME DP - Unbound Medicine ER -