Tekin Neslihan, Ustuner Mehmet C, Akyuz Fahrettin, Ozbayer Cansu S, Aydın Ozlem, Benkli Kadriye, Burukoglu Dilek, Degirmenci Irfan, Ozden Hilmi
Department of Chemistry, Biochemistry Division, Faculty of Arts and Science, Aksaray University, Aksaray, Turkey,
Mol Biol Rep. 2014 Aug;41(8):5109-21. doi: 10.1007/s11033-014-3376-2. Epub 2014 Apr 23.
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.
我们评估了二吡啶并[3,2 - a:2',3' - c]吩嗪（dppz）金（III）配合物（[Au(dppz)Cl₂]Cl）在化学诱导的肝细胞癌过程中对细胞凋亡的影响。48只雄性斯普拉格 - 道利大鼠被分为六组；第一组（对照组），第二组[二甲基亚砜（DMSO）]，第三组（[Au(dppz)Cl₂]Cl），第四组[二乙基亚硝胺 + 苯巴比妥（DEN + PB）]，第五组（DEN + PB + [Au(dppz)Cl₂]Cl（第2周）），以及第六组（DEN + PB + [Au(dppz)Cl₂]Cl（第7周））。第四组至第六组的大鼠腹腔注射单剂量175 mg/kg的DEN。给予DEN两周后，这些组的大鼠每天给予剂量为500 ppm的PB。在第五组中，给予DEN两周后，通过腹腔注射每周一次给予[Au(dppz)Cl₂]Cl配合物（2 mg/kg）。在第六组中，给予DEN七周后，大鼠每周一次给予剂量为2 mg/kg的[Au(dppz)Cl₂]Cl配合物。在研究结束时，从大鼠收集血液和组织样本，以测定血清AST、ALT和LDH水平，以及肝脏中caspase 3、p53、Bax、Bcl - 2和DNA片段化情况。与第一组相比，第四组的AST、ALT、LDH和Bcl - 2水平较高，但caspase 3和p53水平较低。在第五组中，caspase 3、p53、Bax和DNA片段化水平高于第四组。与第四组相比，第六组中caspase 3和p53水平升高。总之，[Au(dppz)Cl₂]Cl配合物通过提高caspase 3、p53、Bax和DNA片段化水平诱导细胞凋亡。
