Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to oxidative stress, nitric oxide pathway and homocysteine

Life Sci. 2007 Jun 20;81(2):121-7. doi: 10.1016/j.lfs.2007.04.027. Epub 2007 May 6.


Hypercholesterolemia is characterized with changes in lipid profile, nitric oxide pathway and oxidative stress markers. This study is designed to evaluate the effects of hypercholesterolemic diet and atorvastatin therapy on oxidative stress, lipid peroxide and thiobarbituric acid reactive substances (TBARS), NO pathway markers, nitric oxide(NO) and asymmetric dimethylarginine (ADMA), homocysteine, and paraoxonase activity (PON1) in rabbits. Twenty rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups on the fourth week of the hypercholesterolemic diet. First group was fed with high-cholesterol diet alone, whereas the second group with the same cholesterol diet plus atorvastatin (0.3 mg/kg/day) for 4 weeks. High-cholesterol diet increased total cholesterol, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), ADMA, TBARS and lipid peroxide levels and reduced PON1 activity and NO levels in rabbits. Four weeks of atorvastatin therapy significantly increased HDL-C, PON1 activity and reduced LDL-C, TBARS and lipid peroxide concentrations. Atorvastatin therapy is beneficial in decreasing oxidative stress related with hypercholesterolemia, mainly affecting lipid profile and PON1 activity.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Aryldialkylphosphatase / metabolism
  • Atorvastatin
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diet
  • Heptanoic Acids / therapeutic use*
  • Homocysteine / metabolism*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism*
  • Lipid Peroxidation / drug effects
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Oxidative Stress / drug effects*
  • Pyrroles / therapeutic use*
  • Rabbits
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Triglycerides / blood


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Thiobarbituric Acid Reactive Substances
  • Triglycerides
  • Homocysteine
  • Nitric Oxide
  • N,N-dimethylarginine
  • Arginine
  • Atorvastatin
  • Nitric Oxide Synthase
  • Aryldialkylphosphatase