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. CONCLUSION: 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.
Subject(s)
Antioxidants/pharmacology , Aortic Diseases/prevention & control , Atherosclerosis/prevention & control , Heptanoic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hypercholesterolemia/drug therapy , Lipoproteins, LDL/metabolism , Plaque, Atherosclerotic/prevention & control , Pyrroles/pharmacology , Animals , Aorta/drug effects , Aorta/metabolism , Aortic Diseases/etiology , Aortic Diseases/metabolism , Aortic Diseases/pathology , Aryldialkylphosphatase/metabolism , Atherosclerosis/etiology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atorvastatin , Catalase/metabolism , Disease Models, Animal , Erythrocytes/drug effects , Erythrocytes/metabolism , Hypercholesterolemia/complications , Hypercholesterolemia/metabolism , Hypercholesterolemia/pathology , Lipid Peroxidation/drug effects , Male , Oxidation-Reduction , Plaque, Atherosclerotic/etiology , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/pathology , Rabbits , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Time FactorsABSTRACT
The periosteum has an important role in bone regeneration. The purpose of this study was to evaluate and compare the osteogenic capacities of tibial and cranial periosteum. To achieve this, 44 New Zealand male rabbits were divided into two groups, each consisting of 22 rabbits. In group 1, periosteal flaps were prepared on the tibia of the posterior cruris of each side. In group 2, bilateral periosteal flaps were prepared on the cranial region. New bone formation was estimated quantitatively by measuring the alkaline phosphatase and osteocalcin levels, because they are the indicators of osteoblastic activity. At weeks 1, 2, 4, and 8, biopsies were taken from five animals of each group for biochemical analyses, and at weeks 2 and 8, biopsies were taken for histologic evaluation. Higher alkaline phosphatase and osteocalcin levels were evaluated in group 1, and more bone formation was observed in group 1. The results showed that osteogenic capacity is higher in tibial periosteum than cranial periosteum.
