Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage.
OBJECTIVE
High-density lipoprotein (HDL)-associated antioxidant paraoxonase (PON) may reduce low-density lipoprotein (LDL) oxidation and prevent atherosclerosis. The aim of this present study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin on hydrogen-peroxide-induced DNA damage by comet assay and the correlation between oxidative DNA damage and antioxidant PON activity.


METHODS
Thirteen type-II/a hyperlipidemic patients were enrolled in the study. We examined the effect of 10 mg/day atorvastatin treatment on lipid levels and the degree of DNA damage in lymphocytes separated from hyperlipidemic patients, nitric oxide (NO), thiobarbituric acid-reactive substances (TBARS), PON levels and activity.


RESULTS
After 6 months, atorvastatin treatment significantly decreased serum cholesterol and LDL-cholesterol levels. The triglyceride level did not change, and there was no significant change in the HDL cholesterol level. The visual score characteristic to the degree of DNA damage in comet assay was significantly decreased, as well as the TBARS level, while the level of NO was non-significantly increased. PON activity and the PON/HDL ratio were significantly increased after atorvastatin treatment. There was a negative correlation between DNA damage and PON activity, as well as between DNA damage and the PON/HDL ratio before and after atorvastatin treatment.


CONCLUSIONS
These findings show that atorvastatin treatment favorably affected the lipid profile, increasing the activity of HDL-associated PON and decreasing the cytotoxic effect of oxidative stress.
Harangi
Mariann
M
1st Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Seres
Ildikó
I
Varga
Zsuzsa
Z
Emri
Gabriella
G
Szilvássy
Zoltán
Z
Paragh
György
G
Remenyik
Eva
E
D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000378:metabolism; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood*; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D017392:Thiobarbituric Acid Reactive Substances; D002784:Cholesterol; D000069059:Atorvastatin; D006861:Hydrogen Peroxide; D043303:Aryldialkylphosphatase