Genotoxicity evaluation of HMG CoA reductase inhibitor rosuvastatin

Abstract

The genotoxic potential of rosuvastatin as one of the statin drugs was assessed by chromosomal aberrations (CAs), micronucleus (MN) and DNA damage by comet assay in the human peripheral blood lymphocytes. Rosuvastatin was used at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 µg/mL for these in vitro assays. In all assays, a negative and positive control were also included. CA frequencies were significantly increased in all concentrations at 24 hours and significantly increased in all concentrations except 0.0625 µg/mL at 48 hours, compared to the negative control. Rosuvastatin has a decreased mitotic index (MI) at 0.5- and 1-µg/mL concentrations at 24 hours and at 0.25, 0.5 and 1 µg/mL at 48 hours. A significant increase was observed for induction of MN in all treatments, compared to the negative control. Cytokinesis-block proliferation indices were not affected by treatments with rosuvastatin. In the comet assay, significant increases in comet tail length and tail moment were observed at 0.0625-, 0.5- and 1-µg/mL concentrations. Comet intensity was significantly increased in all concentrations except 0.0625 µg/mL. According to these results, rosuvastatin is cytotoxic and clastogenic/aneugenic in human peripheral lymphocytes. Further studies should be conducted in other test systems to evaluate the full genotoxic potential of rosuvastatin.

Therapeutic effects of statins on chromosomal DNA damage of dyslipidemic patients

“…But the results of these studies are contradictory; it was found that atorvastatin significantly decreased MN frequency induced by ionizing radiation in human lymphocytes, 29 while rosuvastatin significantly increased MN frequency at all concentrations in human lymphocytes. 30…”

“…Similarly, an in vitro study had shown that rosuvastatin decreased the cytokinesis-block proliferation indices in human peripheral blood lymphocytes, but this effect was not statistically significant. 30…”

Effect of Simvastatin on Male Albino Rats, Cytogenetic and Histochemical Studies

“…It is worthmentioning that statins may have an influence on genomic damage (Pernice et al, 2006). Some types of statins such as rosuvastatin can be considered cytotoxic in human peripheral lymphocytes (Berber et al, 2014) since it may increase the chromosomal aberration frequencies.…”

Avaliação do efeito modulador de diferentes estatinas sobre danos ao DNA induzidos pela doxorrubicina em células somáticas de Drosophila melanogaster

“…A recent study conducted by Berber et al (2014) showed that rosuvastatin presented genotoxic effects based on results obtained through the evaluation of chromosomal aberrations, micronuclei and damage to DNA (comet assay). These results should be considered, especially since they were observed in human peripheral lymphocytes.…”