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-Lipoic Acid Prevents the Increase in Atherosclerosis Induced by Diabetes in Apolipoprotein E–Deficient Mice Fed High-Fat/Low-Cholesterol Diet

From the Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Address correspondence and reprint requests to Dr. Nobuyo Maeda, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 701 Brinkhous-Bullitt Bldg., Chapel Hill, NC 27599-7525. E-mail: nobuyo{at}med.unc.edu

Abbreviations: apo, apolipoprotein; STZ, streptozotocin; TBARS, thiobarbituric acid reactive substance

Considerable evidence indicates that hyperglycemia increases oxidative stress and contributes to the increased incidence of atherosclerosis and cardiovascular complications in diabetic patients. To examine the effect of -lipoic acid, a potent natural antioxidant, on atherosclerosis in diabetic mice, 3-month-old apolipoprotein (apo) E-deficient (apoE^–/–) mice were made diabetic by administering streptozotocin (STZ). At 4 weeks after starting the STZ administration, a high-fat diet with or without -lipoic acid (1.65 g/kg) was given to the mice and to nondiabetic apoE^–/– controls. At 20 weeks, markers of oxidative stress were significantly lower in both the diabetic apoE^–/– mice and their nondiabetic apoE^–/– controls with -lipoic acid supplement than in those without it. Remarkably, -lipoic acid completely prevented the increase in plasma total cholesterol, atherosclerotic lesions, and the general deterioration of health caused by diabetes. These protective effects of -lipoic acid were accompanied by a reduction of plasma glucose and an accelerated recovery of insulin-producing cells in the pancreas, suggesting that part of its effects are attributable to protecting pancreatic ß-cells from damage. Our results suggest that dietary -lipoic acid is a promising protective agent for reducing cardiovascular complications of diabetes.

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