Cardiac lipids and antioxidant status in high fructose rats and the effect of alpha-lipoic acid.

BACKGROUND AND AIMS: The development of insulin resistance has been shown to be an early step in the development of cardiovascular diseases in diabetic patients. Oxidative stress may be important in the development of coronary artery disease. Fructose loaded rats, which show the characteristic features of insulin resistance, also display an imbalance between the peroxidation process and the antioxidant system. Alpha-lipoic acid (LA)--a co-enzyme--is known for its potent antioxidant effects. The present study examined whether LA mitigates fructose-induced oxidative stress in heart tissue.

METHODS AND RESULTS: Male Wistar rats with a body weight of 150-170g were divided into 4 groups of 6 rats each. Control rats received a control diet containing starch and water ad libitum. Fructose rats received a fructose-enriched diet (>60% of total calories). Fructose + LA rats received a fructose diet and alpha-lipoic acid (35mg/kg b.w i.p.). Control + LA rats received control diet and alpha-lipoic acid. After the 20-day treatment period, we assessed the insulin sensitivity index in terms of HOMA. The levels of lipid peroxidation markers and the enzymatic and non-enzymatic antioxidant status in the heart tissue were measured. Plasma and heart tissue lipids were also analysed. Fructose rats showed decreased insulin sensitivity as reflected by high values of HOMA, increased peroxidation, impaired antioxidant status and lipid abnormalities in the cardiac tissue. These abnormalities were attenuated and the antioxidant levels were enhanced by LA. The reduction in HOMA values suggests LA improves insulin sensitivity.

CONCLUSIONS: Improvement of insulin sensitivity and enhancement of cardiac antioxidant status suggest that LA may be useful as a cardioprotective agent in insulin-resistant states.