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

Abstract

We evaluated the effects of dipyrido [3,2-a:2-,3--c] phenazine (dppz) Au(III) complex ([Au(dppz)Cl-2]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)Cl-2]Cl), group IV [diethylnitrosamine + Phenobabital (DEN + PB)], group V (DEN + PB + [Au(dppz)Cl-2]Cl (2nd week)), and group VI (DEN + PB + [Au(dppz)Cl-2]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)Cl-2]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)Cl-2]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)Cl-2]Cl complex induced apoptosis by elevating levels of caspase 3, p53, Bax, and DNA fragmentation.