alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet.
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 alpha-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 alpha-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 alpha-lipoic acid supplement than in those without it. Remarkably, alpha-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 alpha-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 beta-cells from damage. Our results suggest that dietary alpha-lipoic acid is a promising protective agent for reducing cardiovascular complications of diabetes.
Yi
Xianwen
X
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 701 Brinkhous-Bullitt Bldg., 27599-7525, USA.
Maeda
Nobuyo
N
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001057:Apolipoproteins E / Q000172:deficiency*; D043303:Aryldialkylphosphatase / Q000097:blood; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004912:Erythrocytes / Q000737:chemistry; D005978:Glutathione / Q000097:blood; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D008063:Thioctic Acid / Q000008:administration & dosage*
D000975:Antioxidants; D001057:Apolipoproteins E; D015415:Biomarkers; D001786:Blood Glucose; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D008063:Thioctic Acid; D043303:Aryldialkylphosphatase; D005978:Glutathione