Effects of Alpha-Lipoic Acid on the Development of Arterial Hypertension, Type 2 Diabetes, Obesity and Vascular Oxidative Stress in Zucker Diabetic Fatty Rats.

El Midaoui, Adil; De Champlain, Jacques; Sadi, Almuktafi; Husain, Mansoor; Fantus, I. George

The aim of the present study was to investigate whether a dietary supplementation of α-lipoic acid could prevent arterial hypertension, insulin resistance, body weight gain and the increase in aorta superoxide anion (0[sub 2-]) production in Zucker diabetic fatty (ZDF) rats. At age 6 weeks, obese male ZDF rats and their lean male counterparts rats were treated with a chow diet supplemented with alpha-lipoic acid (1g/kg feed) during 6 weeks. Oxidative stress was evaluated by measuring the aortic O2- production using the lucigenin method. In comparison to lean Zucker rats, ZDF rats exhibited significant increases in body weight (P<0.01), in systolic blood pressure (P<0.05), in blood insulin and glucose levels (P<0.01), in insulin resistance index (P<0.01), in epididymal fat and pancreas weights per body weight (P<0.05) and in basal 02-production (P<0.05) as well as in NADPH oxidase activity in aortic tissue. The simultaneous supplementation diet with lipoic acid (LA) prevented the development of arterial hypertension, the rise in body weight (P<0.05) and the increase in basal 02- production (P<0.05) as well as in NADPH oxidase activity (P<0.01) in aortic tissue in ZDF rats. Moreover, LA decreased significantly (P<0.01) the epididymal fat weight per body weight in ZDF rats. LA only modestly attenuated the blood glucose levels as well as the insulin resistance index in ZDF rats. These findings demonstrate that LA, a potent antioxidant, was efficacious in preventing the increase in blood pressure and body weight in ZDF rats. The antihypertensive effect of LA is associated with a decrease in vascular oxidative stress as reflected by the decrease in basal 02-production as well as the NADPH oxidase activity in aortic tissue in ZDF rats. The weaker effect of LA on insulin resistance and blood glucose indicate that factors other than oxidative stress contribute significantly to the metabolic derangement in the ZDF rats.

LIPOIC acid; CARDIOVASCULAR disease prevention; HYPERTENSION; INSULIN resistance; OBESITY; OXIDATIVE stress; TYPE 2 diabetes; PEOPLE with diabetes; LABORATORY rats

Diabetes, 2007, Vol 56, pA193

0012-1797

Academic Journal