Effect of atorvastatin and ezetimibe treatment on serum lipid profile and oxidative state in rats fed with a high-cholesterol diet.
BACKGROUND
The effects of ezetimibe and atorvastatin on serum lipid profile and oxidant-antioxidant system were investigated in rats.


METHODS
Seventy-two Sprague-Dawley rats were assigned to 6 groups. Group 1 was fed with standard rat chow. Group 2 and the other 4 groups were fed with a high-cholesterol diet: 10 mg/kg/d atorvastatin to group 3; 1 mg/kg/d atorvastatin to group 4; 10 mg/kg/d atorvastatin and 1 mg/kg/d ezetimibe to group 5; and 1 mg/kg/d ezetimibe to group 6. After 3 months, serum total, low-density lipoprotein, high-density lipoprotein cholesterol, and triglyceride levels, and the activities of malondialdehyde, glutathione peroxidase, and superoxide dismutase were measured in the plasma. In addition, the left anterior descending and femoral arteries were examined histopathologically.


RESULTS
Serum total, low-density lipoprotein cholesterol, and triglyceride levels decreased slightly in group 3. However, administration of 1 mg/kg/d atorvastatin or 1 mg/kg/d ezetimibe did not significantly change lipid parameters. Plasma malondialdehyde levels slightly increased in group 2 compared with controls and decreased compared with both the atorvastatin regimens. However, malondialdehyde levels increased with the addition of ezetimibe to atorvastatin. Only the administration of ezetimibe significantly elevated the levels of malondialdehyde. Glutathione peroxidase and superoxide dismutase levels were also found to be significantly reduced in the groups receiving ezetimibe when compared with atorvastatin groups.


CONCLUSIONS
Atorvastatin has a beneficial effect on oxidative stress in rats fed with high-cholesterol diet. A combination of ezetimibe with atorvastatin diminishes the beneficial effects of atorvastatin. Conversely, the sole administration of ezetimibe increases oxidative stress.
Departments of Cardiovascular Surgery, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. alpyasim@ksu.edu.tr
Alptekin
A
Yasim
Davut
D
Ozbag
Metin
M
Kilinc
Harun
H
Ciralik
Harun
H
Toru
Yakup
Y
Gümüşalan
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001384:Azetidines / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D000069438:Ezetimibe; D005979:Glutathione Peroxidase / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D008315:Malondialdehyde / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000924:Anticholesteremic Agents; D001384:Azetidines; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D008315:Malondialdehyde; D000069059:Atorvastatin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000069438:Ezetimibe