Topaktas M, Kafkas N E, Sadighazadi S, Istifli E S
Department of Biology, Faculty of Science and Letters, Cukurova University, 01330, Adana, Turkey.
Department of Horticulture, Faculty of Agriculture, Cukurova University, 01330, Adana, Turkey.
Cytotechnology. 2017 Aug;69(4):579-589. doi: 10.1007/s10616-017-0069-4. Epub 2017 Jan 17.
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 325 μg/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.
苯扎贝特（BF）是一种过氧化物酶体增殖物激活受体（PPAR）激动剂，用作降脂药物，用于治疗家族性或获得性混合型高脂血症。BF是唯一一种作用于α、β和δ所有PPAR亚型的贝特类药物。尽管有研究表明使用贝特类药物存在潜在的遗传毒性，但据我们所知，尚未对BF在人外周血淋巴细胞中的遗传毒性进行研究。在本研究中，使用染色体畸变（CA）和微核（MN）试验，在健康人类受试者的外周血淋巴细胞中评估了BF的遗传毒性潜力。此外，还使用高效液相色谱（HPLC）方法来鉴定和定量药物进入细胞的情况。将人外周血淋巴细胞暴露于四种不同浓度（100、175、250和325μg/mL）的BF中，处理24小时和48小时。如HPLC所示，尽管在24小时和48小时的处理期间BF大量进入人外周血淋巴细胞，但未发现BF会增加CA和MN频率。另一方面，将细胞暴露于BF中24小时和48小时，导致有丝分裂指数（24小时：r = -0.995，p < 0.01；48小时：r = -0.992，p < 0.01）和核分裂指数（24小时：r = -0.990，p < 0.01；48小时：r = -0.981，p < 0.01）出现显著的浓度依赖性下降。我们的结果表明，BF对培养的人外周血淋巴细胞具有细胞毒性作用。
