gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Reduction of oxidative stress and DNA damage by rosuvastatin in human promyelocytic HL-60 cells

Reduktion von oxidativem Stress und DNA-Schäden durch Rosuvastatin in humanen promyelocytischen HL-60 Zellen

Meeting Abstract

  • N. Schupp - Universität Würzburg (Würzburg, D)
  • U. Schmid - Universität Würzburg (Würzburg, D)
  • E. Arnold - Universität Würzburg (Würzburg, D)
  • A. Heidland - Universität Würzburg (Würzburg, D)
  • H. Stopper - Universität Würzburg (Würzburg, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP51

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch051.shtml

Veröffentlicht: 8. August 2006

© 2006 Schupp et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, exert various beneficial effects independently of serum cholesterol reduction, among others by antioxidative action. Human promyelocytic cells (HL-60) were used to examine the effect of the new statin rosuvastatin on reactive oxygen species (ROS)-induced DNA damage, formation of oxidative stress and expression of NADPH oxidase subunits.

Methods and Results: DNA damage caused by phorbol 12-myristate 13-acetate (PMA) or by hydrogen peroxide (H2O2) was assessed by the comet assay. The protein kinase C activator fMLP was used to provoke the formation of micronuclei, a second parameter to measure DNA damage. Oxidative stress induced by PMA was measured by flow cytometry. The effect of PMA and rosuvastatin on the expression of the subunits of the phagocytic NADPH oxidase was analysed by RT-PCR.

DNA damage induced by PMA or by H2O2 was reduced to control values by the addition of 10 nM rosuvastatin. Also micronuclei, induced by fMLP, were reduced by co-incubation with 10 microM rosuvastatin. PMA-provoked formation of ROS was prevented by 1 microM rosuvastatin. RT-PCR showed that the expression of the NADPH oxidase subunits p47, p67 and gp91 was increased by PMA, but not reversed by 1 microM rosuvastatin. Intermediates of the cholesterol synthesis pathway could not reverse the reduction of DNA damage by rosuvastatin or the prevention of ROS formation.

Conclusion: Rosuvastatin, in a concentration comparable to plasma levels in therapy, shows an antioxidative effect which is also capable of preventing DNA damage. This effect seems to be independent of HMG-CoA reductase inhibition.