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Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage

  • Pharmacodynamics
  • Published:
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Abstract

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.

Conclusion

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.

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Acknowledgements

This study was supported by a grant from OTKA (Hungarian Scientific Research Fund) (T032674), and ETT (Medical Research Council) (107/2001), Hungary.

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Authors and Affiliations

  1. 1st Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Mariann Harangi, Ildikó Seres, Zsuzsa Varga & György Paragh

  2. Department of Dermatology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4012, Debrecen, Hungary

    Gabriella Emri & Éva Remenyik

  3. Department of Pharmacology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Zoltán Szilvássy

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  1. Mariann Harangi
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  2. Ildikó Seres
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Correspondence to Éva Remenyik.

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Harangi, M., Seres, I., Varga, Z. et al. Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage. Eur J Clin Pharmacol 60, 685–691 (2004). https://doi.org/10.1007/s00228-004-0820-6

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  • DOI: https://doi.org/10.1007/s00228-004-0820-6

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