Molecular Biology Reports

, Volume 41, Issue 8, pp 5109–5121

Apoptotic effects of dipyrido [3,2-a:2′,3′-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats

Authors

    • Department of Chemistry, Biochemistry Division, Faculty of Arts and ScienceAksaray University
  • Mehmet C. Ustuner
    • Department of Medical Biology, Faculty of MedicineEskisehir Osmangazi University
  • Fahrettin Akyuz
    • Department of Medical Biochemistry, Faculty of MedicineEskisehir Osmangazi University
  • Cansu S. Ozbayer
    • Department of Medical Biology, Faculty of MedicineEskisehir Osmangazi University
  • Ozlem Aydın
    • Department of Medical Biochemistry, Faculty of MedicineEskisehir Osmangazi University
  • Kadriye Benkli
    • Department of Pharmaceutical Chemistry, Faculty of PharmacyAnadolu University
  • Dilek Burukoglu
    • Department of Histology, Faculty of MedicineEskisehir Osmangazi University
  • Irfan Degirmenci
    • Department of Medical Biology, Faculty of MedicineEskisehir Osmangazi University
  • Hilmi Ozden
    • Department of Anatomy, Faculty of MedicineEskisehir Osmangazi University
Article

DOI: 10.1007/s11033-014-3376-2

Cite this article as:
Tekin, N., Ustuner, M.C., Akyuz, F. et al. Mol Biol Rep (2014) 41: 5109. doi:10.1007/s11033-014-3376-2

Abstract

We evaluated the effects of dipyrido [3,2-a:2′,3′-c] phenazine (dppz) Au(III) complex ([Au(dppz)Cl2]Cl) on apoptosis during chemically induced hepatocellular carcinoma. 48 male Spraque-Dawley rats were divided into six groups; group I (control), group II [Dimethyl sulfoxide (DMSO)], group III ([Au(dppz)Cl2]Cl), group IV [diethylnitrosamine + Phenobabital (DEN + PB)], group V (DEN + PB + [Au(dppz)Cl2]Cl (2nd week)), and group VI (DEN + PB + [Au(dppz)Cl2]Cl (7th week). The rats in groups IV through VI were administrated with DEN in a single dose of intraperitoneal 175 mg/kg. After 2 weeks of DEN administration, these groups of rats were given daily PB in a dose of 500 ppm. In group V, after two weeks of DEN administration, [Au(dppz)Cl2]Cl complex (2 mg/kg) was given once a week by intraperitoneal injection. In the group VI, the rats were given a dose of 2 mg/kg [Au(dppz)Cl2]Cl complex once a week, 7 weeks after DEN administration. At the end of the study, blood and tissue samples were collected from the rats to determine levels of serum AST, ALT, and LDH, and caspase 3, p53, Bax, Bcl-2 and DNA fragmentation in liver. AST, ALT, LDH, and Bcl-2 levels were higher in group IV, compared to group I, but caspase 3 and p53 levels were lower. In group V, caspase 3, p53, Bax, and DNA fragmentation levels were higher than those of group IV. Caspase 3 and p53 levels increased in group VI compared with group IV. In conclusion, [Au(dppz)Cl2]Cl complex induced apoptosis by elevating levels of caspase 3, p53, Bax, and DNA fragmentation.

Keywords

Gold(III) complexes Apoptosis Bax Bcl-2 Caspase 3

Abbreviations

dppz

Dipyrido [3,2-a:2′,3′-c] phenazine

[Au(dppz)Cl2]Cl

Dipyrido [3,2-a:2′,3′-c] phenazine (dppz) Au(III)

DMSO

Dimethyl sulfoxide

DEN

Diethylnitrosamine

PB

Phenobarbital

Cisplatin

Cis-diammine-dichloroplatinum (II)

HCC

Hepatocellular carcinoma

TUNEL

Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling

LD50

50 % Lethal dose

SPSS

Statistical package for the social sciences

Copyright information

© Springer Science+Business Media Dordrecht 2014