The protective effects of demethoxyviridine and 1-alpha-hydroxy-demethoxyviridine in the livers of male rats treated with diethylnitrosamine and 2-acetylaminflourene.
ABSTRACT To determine the protective effects of a fungal metabolite of demethoxyviridine (DMV) and its derivative, 1-alpha-hydroxy-DMV in the livers of 2-month-old male Spraque-Dawley rats treated with diethylnitrosamine (DEN) and 2-acetylaminflourene (2-AAF).
This study was performed in the Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey from May 2006. Animals were divided into 10 groups. Those were the control, olive oil, dimethyl sulfoxide (DMSO), DMV, 1-alpha-hydroxy-DMV, DEN, 2-AAF, DEN+2-AAF, DEN+2-AAF+DMV, and DEN+2-AAF+1-alpha-hydroxy-DMV-treated animal groups. The liver microsomes were prepared from rats and the levels of expression of cytochrome P450 1A2 (CYP1A2) enzymes were determined with western blot technique. The liver tissue slides were evaluated histopathologically with hematoxylin and eosin staining and immunohistochemically for Harvey-retrovirus associated DNA sequences (Ha-Ras), glutathione S- transferase (GST-p), and connexion-32 (Cx32) proteins.
Notably, there were no appreciable differences in CYP1A2 level among control, olive oil, and DMSO-treated animals. The CYP1A2 level was significantly decreased in 2-AAF, DEN+2-AAF, DEN, DEN+2-AAF+DMV, DEN+2-AAF+1-alpha-hydroxy-DMV, 1-alpha-hydroxy-DMV, and DMV-treated animals as compared to the control. Most prenoplastic focus was found in DEN+2-AAF treated group.
Demethoxyviridine and 1-alpha-hidroksi-DMV had protective effect in the livers of DEN, 2-AAF and DEN+2-AAF induced 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.Molecular Biology Reports 04/2014; 41(8). DOI:10.1007/s11033-014-3376-2 · 1.96 Impact Factor