Lovastatin prevents bleomycin-induced DNA damage to HepG2 cells

被引:9
作者
Nasiri, Marjan
Etebari, Mahmoud [1 ]
Jafarian-Dehkordi, Abbas
Moradi, Shahla
机构
[1] Isfahan Univ Med Sci, Sch Pharm & Pharmaceut Sci, Dept Pharmacol, Esfahan, Iran
关键词
Bleomycin; Lovastatin; Comet assay; Genotoxicity;
D O I
10.4103/1735-5362.194876
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 mu M) before exposure to BLM (0.5 mu g/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 mu M has genoprotective effect and in doses higher than 50 mu M 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.
引用
收藏
页码:470 / 475
页数:6
相关论文
共 32 条
[1]  
ADAMSON P, 1992, J BIOL CHEM, V267, P20033
[2]   DISCOVERY, BIOCHEMISTRY AND BIOLOGY OF LOVASTATIN [J].
ALBERTS, AW .
AMERICAN JOURNAL OF CARDIOLOGY, 1988, 62 (15) :J10-J15
[3]  
Alberts AW, 1997, NUTR CANC, V29, P127
[4]  
BURGER RM, 1981, LIFE SCI, V28, P715, DOI 10.1016/0024-3205(81)90153-3
[5]   Mechanistic studies on bleomycin-mediated DNA damage: multiple binding modes can result in double-stranded DNA cleavage [J].
Chen, Jingyang ;
Ghorai, Manas K. ;
Kenney, Grace ;
Stubbe, JoAnne .
NUCLEIC ACIDS RESEARCH, 2008, 36 (11) :3781-3790
[6]   Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E, lovastatin and amlodipine [J].
Chen, LY ;
Haught, WH ;
Yang, BC ;
Saldeen, TGP ;
Parathasarathy, S ;
Mehta, JL .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1997, 30 (02) :569-575
[7]   Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: A biphasic experimental study [J].
Chitra, Palanivel ;
Saiprasad, Gowrikumar ;
Manikandan, Ramar ;
Sudhandiran, Ganapasam .
TOXICOLOGY LETTERS, 2013, 219 (02) :178-193
[8]   Lovastatin protects human endothelial cells from the genotoxic and cytotoxic effects of the anticancer drugs doxorubicin and etoposide [J].
Damrot, J. ;
Nuebel, T. ;
Epe, B. ;
Roos, W. P. ;
Kaina, B. ;
Fritz, G. .
BRITISH JOURNAL OF PHARMACOLOGY, 2006, 149 (08) :988-997
[9]   Genotoxicity testing of combined treatment with cisplatin, bleomycin, and 5-fluorouracil in somatic cells of Drosophila melanogaster [J].
Danesi, Cristiane Cademartori ;
Dihl, Rafael Rodrigues ;
Bellagamba, Bruno Correa ;
Rodrigues de Andrade, Heloisa Helena ;
Cunha, Kenya Silva ;
Guimaraes, Nilza Nascimento ;
Lehmann, Mauricio .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2012, 747 (02) :228-233
[10]   Modulation of antioxidant enzymes in bleomycin-treated rats by vitamin C and β-carotene [J].
Desai, VG ;
Lyn-Cook, LE ;
Aidoo, A ;
Casciano, DA ;
Feuers, RJ .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 1997, 29 (02) :127-132