title: Effect of atorvastatin therapy on oxidant-antioxidant status and atherosclerotic plaque formation.
abstract: BACKGROUND
  The aim of this study was to determine the oxidant-antioxidant status and lipid peroxidation products, as well as paraoxonase and atherosclerotic plaque formation, in a hypercholesterolemic atherosclerosis rabbit model to investigate the effects of atorvastatin in the atherosclerotic process.
  
  
  METHODS
  Forty male New Zealand rabbits were divided into four groups, ie, a control group receiving standard pellets, a group receiving atorvastatin therapy, a hypercholesterolemic group receiving an atherogenic diet, and a group receiving both an atherogenic diet and atorvastatin.
  
  
  RESULTS
  The atherogenic diet increased the levels of low-density lipoprotein (LDL) thiobarbituric acid reactive substances (1.84 vs 3.79 nmol/mg protein) and LDL-conjugated diene (147 vs 318 μmol/mg protein) after induction of oxidation by Cu(2+), despite an increase of superoxide dismutase activity. Treatment with atorvastatin limited LDL oxidation significantly (LDL thiobarbituric acid reactive substances 2.19 nmol/mg protein, LDL-conjugated diene 222 μmol/mg protein). Paraoxonase, which prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids, showed a pronounced decrease in the group receiving the atherogenic diet (110 U/L to 28 U/L), and atorvastatin treatment increased paraoxonase activity. Histological examination of arcus aorta tissues from the hypercholesterolemic group showed abundant plaque formation surrounding and obstructing the lumen, whereas treatment with atorvastatin prevented or limited plaque formation, keeping the plaque thin and localized.
  
  
  CONCLUSIONS
  Atorvastatin has dramatic antiatherosclerotic effects, part of which seems to be due to the antioxidant features of the parent drug and/or its metabolites, favoring inhibition of LDL oxidation.
authors: Medical Biochemistry, Department, Ege University School of Medicine, Izmir, Turkey. ebru.sezer@ege.edu.tr
authors: Ebru Demirel
authors: ED
authors: Sezer
authors: Eser Yildirim
authors: EY
authors: Sozmen
authors: Deniz
authors: D
authors: Nart
authors: Taner
authors: T
authors: Onat
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001018:Aortic Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; D017392:Thiobarbituric Acid Reactive Substances; D000069059:Atorvastatin; D002374:Catalase; D013482:Superoxide Dismutase; D043303:Aryldialkylphosphatase