Lovastatin prevents bleomycin-induced DNA damage to HepG2 cells

Abstract

Lovastatin as a member of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors is used as a lipid-lowering agent. It can also inhibit the formation of hydrogen peroxide and superoxide anion and finally leads to decline in oxidative stress processes. Here, we evaluated whether lovastatin can increase DNA damage resistance of HepG2 cells against genotoxicity of the anticancer drug bleomycin (BLM). HepG2 cells were incubated with different concentrations of lovastatin (0.1, 0.5, 1, 5 µM) before exposure to BLM (0.5 µg/mL for one h). The genotoxic dose of BLM and lovastatin was separately determined and comet assay was used to evaluate the genotoxicity. After trapping cells in agarose coated lames, they were lysed and the electrophoresis was done in alkaline pH, then colored and monitored by florescent microscope. The results of this study indicated that lovastatin in doses lower than 5 µM has genoprotective effect and in doses higher than 50 µM is genotoxic. In conclusion, lovastatin is able to protect genotoxic effects of BLM in HepG2 cells. Further studies are needed to elucidate the mechanism(s) involved in this process.

Keywords: Bleomycin; Comet assay; Genotoxicity; Lovastatin.

Fig. 1

Comparison of (A) tail length, (B) %DNA in the tail, and (C) tail moment of different concentrations of lovastatin (0.1, 0.5, 1, and 5 μM) prior to administration of bleomycin (0.5 μg/mL). Data are represented as mean ± SEM. *** and ****s show significant differences (P < 0.001) compared with bleomycin (0.5 μg/mL) group. ## and #### show significant differences (respectively P < 0.01 and P < 0.0001) between lovastatin concentrations.

Fig. 2

Comparison of (A) tail length, (B) %DNA in the tail and (C) tail moment of different concentrations of lovastatin (1, 10, 50, and 100 μM). Data are presented as mean ± SEM. *** shows significance (P < 0.001) compared to control group.