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)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.

Modulatory role of betulinic acid inN-nitrosodimethylamine-induced hepatorenal toxicity in male Wistar rats

“…25,26 NDMA and diethylnitrosamines have been reported to cause hepatic carcinogenesis in animals. 27,28…”

One pot three component synthesis of DNA targeting phototoxic Ru(ii)-p-cymene dipyrido[3,2-a:2′,3′-c]phenazine analogues

“…Molecules like dipyrido[3,2-a:2′,3′-c]phenazine (dppz) based ruthenium complexes have been reported as a potential agent in many biological activities such as antitumour, antimicrobial, antiviral, anti-tuberculosis, and anticancer activities. [1][2][3] The utility of such types of metal complexes is completely based on their enormous DNA intercalating nature, excellent redox behavior, good luminescence properties, and extensive photophysical and electrochemical properties. [4][5][6] Over the past few decades, several methods have been developed for the synthesis of dipyrido[3,2-a:2′,3′-c]phenazine (dppz) based ruthenium and iridium complexes from o-phenylenediamine including the use of several organic solvents (methanol, ethanol, acetonitrile, dichloromethane, DMF, etc.…”

“…a:2′,3′-c] phenazine]PF 6 (RuL2). Yield: 92%; colour: orange; Mp: 178 °C; R f ( pure methanol): 0.61;1 H NMR (CDCl 3 , 400 MHz): δ 10.38 (d, 2H, H-1, H-10, J = 4.4 Hz, ArH), 9.59 (t, 2H, H-3, H-8, J = 8.0 Hz, ArH), 8.25-8.30 (m, 3H, H-2, H-9, H-15, ArH), 7.89 (d, 1H, H-18, J = 2.8 Hz, ArH), 7.73-7.79 (m, 1H, H-16, ArH), 6.52 (d, 2H, H-c, H-d, J = 4.0 Hz, p-cymene ArH), 6.39 (d, 2H, H-e, H-f, J = 5.6 Hz, p-cymene ArH), 2.76-2.82 (m, 1H, H-h, p-cymene aliphatic -CH proton), 2.34 (s, 3H, H-a, p-cymene aliphatic -CH 3 proton), 1.06 (d, 6H, H-i, H-j, J = 6.8 Hz, p-cymene isopropyl -CH 3 protons); 13 C NMR (CDCl 3 , 100 MHz): δ 158.6, 158.4, 151.4, 148.2, 147.9, 140.1, 139.4, 135.7, 135.4, 132.1, 129.8, 129.6, 128.2, 123.8, 112.7, 112.5, 105.5 ( p-cymene ArC), 104.1 ( p-cymene ArC), 87.0 ( p-cymene ArCH), 84.64 ( p-cymene ArCH), 31.3 (isopropyl -CH), 22.3 (isopropyl -CH 3 ), 19.17 (-pcymene -CH 3 ); 19 F NMR (CDCl 3 , 376 MHz): δ −71.07 (PF 6 ), −69.19 (PF 6 ) −61.41 (-F); 31 P NMR (CDCl 3 , 162 MHz): δ −152.99 to −135.43 (PF 6 ); HRMS (MeOH): m/z = 571.0657 [M − PF 6 ] + . Calculated 571.0639; anal.…”

Protective Effect of Silymarin on Liver in Experimental in the Sepsis Model of Rats

“…AST is found in both mitochondria and the cytosol, while ALT is found only in the cytosol [ 66 ]. Therefore, ALT is a more accurate indication of the detection of hepatocellular damage [ 7 , 63 ]. In a study of the literature, in parallel with our findings, in the blood samples of rats with sepsis caused by LPS; it has been reported that ALT, AST, and ALP enzymes were found to be significantly higher in the sepsis group [ 42 ].…”