ANTIOXIDANT EFFECTS OF LOVASTATIN AND VITAMIN-E ON EXPERIMENTAL ATHEROSCLEROSIS IN RABBITS

The effects of the administration of vitamin E (10 mg/day) plus lovast atin (2 mg/day; group A, n = 10), lovastatin alone (2 mg/day; group B, n = 10), and placebo (group C, n = 10) were compared over 24 weeks in a randomized, single-blind controlled trial. All groups of rabbits re ceived a trans fatty acid (TFA)-rich diet (5-10 g/day) for 36 weeks. T reatment with vitamin E pins lovastatin (group A) and lovastatin (grou p B) started after 12 week of administration of TFA-rich diet was asso ciated with a significant but similar decline in serum cholesterol, lo w-density lipoprotein (LDL) cholesterol, and triglycerides in both gro ups at 36 weeks. Lipid peroxides and diene conjugates showed a signifi cant decline in association with a significant increase in the plasma level of vitamin E in group A rabbits at 36 weeks. However, the lovast atin group B showed a lesser but significant decrease in Lipid peroxid es and diene conjugates at 36 weeks, indicating that lovastatin may ha ve antioxidant activity. In control group C, the increase in blood Lip ids and oxidative stress at 36 weeks was much greater than the decreas e in groups A and 11. After experimental lipid peroxidation at 24 week s in all of the rabbits, 2 of 10 group B and 3 of 10 group C rabbits d ied due to coronary thrombosis; there were no deaths in group A. Thus antioxidant therapy with vitamin E can provide protection against deat h due to free radical stress. Aortic Lipids and sudanophilia indicatin g athorosclorosis were significantly lower in groups A and B than in g roup C. The atherosclerotic coronary plaque sizes were significantly s maller in group A (18.5 +/- 3.6 mu m) than in groups B (41.6 +/- 4.2 m u m) and C (85 +/- 6.7 mu m). Aortic plaque sizes were also smaller in group A than in group B and C. It is possible that antioxidant therap y with vitamin E, as an adjunct to lipid lowering with lovastatin, can provide additional benefit in the inhibition of oxidative stress and atherosclerosis. The antioxidant activity of lovastatin has not been r eported, to our knowledge.