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

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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.

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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

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Acknowledgments

This study was supported by Eskisehir Osmangazi University Scientific Research Commission. Contract grants number 201011044.

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Authors and Affiliations

  1. Department of Chemistry, Biochemistry Division, Faculty of Arts and Science, Aksaray University, Aksaray, Turkey

    Neslihan Tekin

  2. Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Mehmet C. Ustuner, Cansu S. Ozbayer & Irfan Degirmenci

  3. Department of Medical Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Fahrettin Akyuz & Ozlem Aydın

  4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey

    Kadriye Benkli

  5. Department of Histology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Dilek Burukoglu

  6. Department of Anatomy, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Hilmi Ozden

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  1. Neslihan Tekin
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Tekin, N., Ustuner, M.C., Akyuz, F. et al. Apoptotic effects of dipyrido [3,2-a:2′,3′-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats. Mol Biol Rep 41, 5109–5121 (2014). https://doi.org/10.1007/s11033-014-3376-2

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