Reduction of oxidative stress and modulation of autoantibodies against modified low-density lipoprotein after rosuvastatin therapy

Br J Clin Pharmacol. 2006 Mar;61(3):262-74. doi: 10.1111/j.1365-2125.2005.02568.x.

Abstract

Aims: To examine the effect of 24 weeks' rosuvastatin treatment on oxidative stress and changes in immune response to oxidized low-density lipoprotein (LDL).

Methods: This was an open-label study of patients in Austria receiving 10 or 40 mg rosuvastatin daily alternately during 12 and 24 weeks. Circulating concentrations of antibodies to malondialdehyde-oxidized LDL (MDA-LDL), both IgG and IgM type, to copper-oxidized LDL (Cu-OxLDL-IgG), concentrations of oxidized LDL complexed to IgG (OxLDL-IC) and markers of oxidative stress and systemic inflammation in subjects with plasma LDL cholesterol concentrations between 130 mg dl-1 and 250 mg dl-1 and triglycerides<or=400 mg dl-1 were determined.

Results: During statin therapy, plasma endogenous peroxides (POX-ACT) concentrations and peroxidase activity were significantly decreased, associated with a modest increase in total antioxidant capacity (TAC). Antibody titres to MDA-LDL-IgM, Cu-OxLDL-IgG and OxLDL-IC decreased, whereas MDA-LDL-IgG concentrations were increased after therapy. These changes were dose- and LDL-independent. POX-ACT concentrations were significantly positively correlated with inflammation markers before and after therapy and inversely with high-density lipoprotein-cholesterol concentrations after therapy.

Conclusion: This study provides in vivo evidence that rosuvastatin significantly reduces oxidative stress and has immunomodulatory properties in a dose- and LDL-independent manner.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Autoantibodies / immunology*
  • Biomarkers / blood
  • Copper / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Fluorobenzenes / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Lipoproteins, LDL / metabolism*
  • Male
  • Malondialdehyde / metabolism
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Peroxidase / metabolism
  • Peroxides / blood
  • Pyrimidines / therapeutic use*
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use*

Substances

  • Antioxidants
  • Autoantibodies
  • Biomarkers
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunoglobulin G
  • Immunoglobulin M
  • Lipoproteins, LDL
  • Peroxides
  • Pyrimidines
  • Sulfonamides
  • Malondialdehyde
  • Copper
  • Rosuvastatin Calcium
  • Peroxidase