Effects of atorvastatin therapy on protein oxidation and oxidative DNA damage in hypercholesterolemic rabbits.
OBJECTIVE
Our aim was to clarify the effects of hypercholesterolemic diet and administeration of atorvastatin on lipid peroxidation, protein oxidation and oxidative DNA damage in male New Zealand white rabbits.


METHODS
We determined malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma. Twenty rabbits were randomly divided into two groups and fed with a high-cholesterol diet (fortified with 1% cholesterol) for 4 weeks. Such rabbits were subjected to either (Group 1) a high-cholesterol diet non-supplemented with atorvastatin (n=10) or (Group 2) a high-cholesterol diet supplemented with atorvastatin (0.3mg atorvastatin per day/kg body weight) for 4 weeks (n=10). A control group (n=5) (Group 3) was fed a cholesterol free diet for 4 weeks. Colorimetric methods were used to determine the level of the oxidative stress markers, except 8-OHdG, which was measured by ELISA.


RESULTS
Rabbits were fed with the high-cholesterol diet alone (Group 1) showed higher levels of lipid profile and oxidative protein and DNA damage than compared with dose of the control group (Group 3). Atorvastatin therapy has substantially beneficial effects on oxidative protein and DNA damage in hypercholesterolemic rabbits.


CONCLUSIONS
The current findings will, we hope, lead to a new insight into the pathogenesis of atherosclerosis. On the other hand inhibition of protein oxidation and DNA oxidation in the plasma by atorvastatin may be one of the pleiotropic effects of statins, and thus the underlying mechanism needs to be further clarifications.
Department of Biochemistry, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey. aydinseval@yahoo.com
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Aydin
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Uzun
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Sozer
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Altug
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D013438:Sulfhydryl Compounds / Q000097:blood / Q000378:metabolism
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000069059:Atorvastatin; D003849:Deoxyguanosine; D005978:Glutathione