In vitro cytogenetic toxicity of bezafibrate in human peripheral blood lymphocytes.

Abstract

Bezafibrate (BF) is a peroxisome proliferator-activated receptor (PPAR) agonist used as a lipid-lowering agent to treat both the familial or acquired combined forms of hyperlipidemia. BF is the only available fibrate drug that acts on all PPAR subtypes of α, β, and δ. Although there are studies that indicate a genotoxic potential associated with the use of fibrates, to our knowledge, the genotoxicity of BF in human peripheral blood lymphocytes has not been studied. In the present study, the genotoxic potential of BF was evaluated using chromosome aberration (CA) and micronucleus (MN) assays in peripheral blood lymphocytes of healthy human subjects. In addition, a high performance liquid chromatography (HPLC) method was used to identify and quantitate the drug passage into the cells. Human peripheral blood lymphocytes were exposed to four different concentrations (100, 175, 250 and 325μg/mL) of BF for 24- and 48-h treatment periods. As shown by HPLC, in spite of significant passage of BF into human peripheral blood lymphocytes in 24- and 48-h treatment periods, BF was not found to increase the CA and MN frequency. On the other hand, exposing cells to BF for 24- and 48-h treatment periods caused significant concentration-dependent decreases in the mitotic index (r=-0.995, p<0.01 for 24-h; r=-0.992, p<0.01 for 48-h) and nuclear division index (r=-0.990, p<0.01 for 24-h; r=-0.981, p<0.01 for 48-h). Our results suggest that BF has cytotoxic effect on cultured human peripheral blood lymphocytes.