The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat.
Oxidative stress and defective fatty acid metabolism in diabetes may lead to impaired nerve perfusion and contribute to the development of peripheral neuropathy. We studied the effects of 2-week treatments with evening primrose oil (EPO; n = 16) or the antioxidant alpha-lipoic acid (ALA; n = 16) on endoneurial blood flow, nerve conduction parameters, lipids, coagulation, and endothelial factors, in rats with streptozotocin-induced diabetes. Compared with their nondiabetic littermates, untreated diabetic rats had impaired sciatic motor and saphenous sensory nerve-conduction velocity (NCV; P <.001), reduced endoneurial blood flow (P <.001), and increased serum triglycerides (P <.01), cholesterol (P < 0.01), plasma factor VII (P <.0001), and von Willebrand factor (vWF; P <.0001). Plasma fibrinogen and serum high-density lipoprotein concentrations were not significantly different. Treatment with either ALA or EPO effectively corrected the deficits in NCV and endoneurial blood flow. ALA was associated with marked and statistically significant decreases in fibrinogen, factor VII, vWF, and triglycerides (P <.01, paired t tests before v after treatment). In contrast, EPO was associated with significant (P <.05) increases in fibrinogen, factor VII, vWF, triglycerides, and cholesterol and a significant decrease in high-density lipoprotein. Changes in levels of coagulation factors and lipids, qualitatively similar to those found with EPO, were obtained with a diet containing sunflower oil (to control for calorific and lipid content) or with a normal diet alone. Blood glucose and hematocrit levels were not significantly altered by treatments. These data suggest that although both ALA and EPO improve blood flow and nerve function, their actions on vascular factors differ. The marked effects of ALA in lowering lipid and hemostatic risk factors for cardiovascular disease indicate potential antithrombotic and antiatherosclerotic actions that could be of benefit in human diabetes and merit further study.
Ford
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I
Departments of Medicine & Therapeutics, University of Aberdeen, Aberdeen, Scotland.
Cotter
M A
MA
Cameron
N E
NE
Greaves
M
M
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005228:Fatty Acids, Essential / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects*; D008041:Linoleic Acids; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D031665:Oenothera biennis; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology; D010938:Plant Oils; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013311:Streptozocin; D008063:Thioctic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*; D017965:gamma-Linolenic Acid
D005228:Fatty Acids, Essential; D008041:Linoleic Acids; D010938:Plant Oils; D014280:Triglycerides; C028498:evening primrose oil; D013311:Streptozocin; D008063:Thioctic Acid; D017965:gamma-Linolenic Acid; D002784:Cholesterol