Antioxidant effects of lovastatin and vitamin E on experimental atherosclerosis in rabbits.
The effects of the administration of vitamin E (10 mg/day) plus lovastatin (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 received a trans fatty acid (TFA)-rich diet (5-10 g/day) for 36 weeks. Treatment with vitamin E plus lovastatin (group A) and lovastatin (group B) started after 12 weeks of administration of TFA-rich diet was associated with a significant but similar decline in serum cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in both groups at 36 weeks. Lipid peroxides and diene conjugates showed a significant decline in association with a significant increase in the plasma level of vitamin E in group A rabbits at 36 weeks. However, the lovastatin group B showed a lesser but significant decrease in lipid peroxides and diene conjugates at 36 weeks, indicating that lovastatin may have antioxidant activity. In control group C, the increase in blood lipids and oxidative stress at 36 weeks was much greater than the decrease in groups A and B. After experimental lipid peroxidation at 24 weeks in all of the rabbits, 2 of 10 group B and 3 of 10 group C rabbits died due to coronary thrombosis; there were no deaths in group A. Thus antioxidant therapy with vitamin E can provide protection against death due to free radical stress. Aortic lipids and sudanophilia indicating athorosclorosis were significantly lower in groups A and B than in group C. The atherosclerotic coronary plaque sizes were significantly smaller in group A (18.5 +/- 3.6 microns) than in groups B (41.6 +/- 4.2 microns) and C (85 +/- 6.7 microns). Aortic plaque sizes were also smaller in group A than in group B and C. It is possible that antioxidant therapy 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 reported, to our knowledge.
Singh
R B
RB
Heart Research Laboratory, Medical Hospital and Research Centre, Moradabad, India.
Singh
N K
NK
Rastogi
S S
SS
Wander
G S
GS
Aslam
M
M
Onouchi
Z
Z
Kummerow
F A
FA
Nangia
S
S
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008148:Lovastatin / Q000627:therapeutic use*; D011817:Rabbits; D016037:Single-Blind Method; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014810:Vitamin E; D002784:Cholesterol; D008148:Lovastatin