Heavy metals, typified by arsenite (As(III)), have been implicated in altering the carcinogenicity of aryl hydrocarbon receptor (AhR) ligands, typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), by modulating the induction of the Cyp1a1 enzyme, but the mechanism remains unresolved. In this study, the effects of As(III) on Cyp1a1 expression and activity were investigated in C57BL/6 mouse livers and isolated hepatocytes. For this purpose, C57BL/6 mice were injected intraperitoneally with As(III) (12.5 mg/kg) in the absence and presence of TCDD (15 μg/kg) for 6 and 24 h. Furthermore, isolated hepatocytes from C57BL/6 mice were treated with As(III) (1, 5, and 10 μM) in the absence and presence of TCDD (1 nM) for 3, 6, 12, and 24 h. At the in vivo level, As(III) decreased the TCDD-mediated induction of Cyp1a1 mRNA at 6h while potentiating its mRNA, protein, and catalytic activity levels at 24 h. At the in vitro level, As(III) decreased the TCDD-mediated induction of Cyp1a1 mRNA in a concentration- and time-dependent manner. Moreover, As(III) decreased the TCDD-mediated induction of Cyp1a1 protein and catalytic activity levels at 24 h. Interestingly, As(III) increased the serum hemoglobin (Hb) levels in animals treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone, there was an increase in the nuclear accumulation of AhR and AhR-dependent luciferase activity. Furthermore, Hb potentiated the TCDD-induced AhR-dependent luciferase activity. Importantly, when isolated hepatocytes were treated for 5h with As(III) in the presence of TCDD and the medium was then replaced with new medium containing Hb, there was potentiation of the TCDD-mediated effect. Taken together, these results demonstrate for the first time that there is a differential modulation of the TCDD-mediated induction of Cyp1a1 by As(III) in C57BL/6 mouse livers and isolated hepatocytes. Thus, this study implicates Hb as an in vivo-specific modulator.

The paper attempt a closer investigation to re-interpret the role of CSR in limiting the extreme practices in earnings management (EM), using evidence from large UK companies.

The 5-(2-phenylhydrazono)-3,3-dimethylcyclohexanone (PHDMC) is synthesized by reacting 5,5-dimethylcyclohexane-1,3-dione with 2-phenylhydrazine. Synthesized PHDMC is polycrystalline with monoclinic space group, P2₁/a. Miller’s indices values for each diffraction peak in the X-ray diffraction spectrum are calculated. Thin films of PHDMC with different thickness values (0.83–1.247μm) are prepared by thermal evaporation technique and they exhibit amorphous structure. Different vibrational modes, observed in infrared spectra of the powder and thin films, were assigned to the molecular bonding structure of PHDMC compound. The optical properties of PHDMC thin films are investigated by measuring the optical transmittance and reflectance at the normal incidence of the light in the spectral range 200–2500nm. The refractive and absorption indices of the films are found to be independent of the film thickness …

In the current study C57BL/6J mice were injected intraperitoneally with Hg(2+) in the absence and presence of TCDD. After 6 and 24h the liver was harvested and the expression of Cyps was determined. In vitro, isolated hepatocytes were incubated with TCDD in the presence and absence of Hg(2+). At the in vivo level, Hg(2+) significantly decreased the TCDD-mediated induction of Cyps at 6h while potentiating their levels at 24h. In vitro, Hg(2+) significantly inhibited the TCDD-mediated induction of Cyp1a1 in a concentration- and time-dependent manner. Interestingly, Hg(2+) increased the serum hemoglobin (Hb) levels in mice treated for 24h. Upon treatment of isolated hepatocytes with Hb alone, there was an increase in the AhR-dependent luciferase activity with a subsequent increase in Cyp1a1 protein and catalytic activity levels. Importantly, when hepatocytes were treated for 2h with Hg(2+) in the presence of TCDD, then the medium was replaced with new medium containing Hb, there was potentiation of the TCDD-mediated effect. In addition, Hg(2+) increased heme oxygenase-1 (HO-1) mRNA, which coincided with a decrease in the Cyp1a1 activity level. When the competitive HO-1 inhibitor, tin mesoporphyrin was applied to the hepatocytes there was a partial restoration of Hg(2+)-mediated inhibition of Cyp1a1 activity. In conclusion, we demonstrate for the first time that there is a differential modulation of the TCDD-mediated induction of Cyp1a1 by Hg(2+) in C57BL/6J mice livers and isolated hepatocytes. Moreover, this study implicates Hb as an in vivo specific modulator of Cyp1 family.

New Synthetic Routes of Functionally substituted[1,2,4][1,5-a]Triazoloquinoline, Coumarinimine, Quinoline, Chromene, Quinazoline, Pyrazoloquinazoline and Benzotriazolotriazine …

SEVERAL new functionally [1,2,4]triazolo[1,5-a]quinoline-4- …… carbonitriles (8a-c) and [1,2,4] triazolo[1,5-a]quinoline-4-carbox-amides 12a,b were prepared from Nʹ-(5,5-dimethyl-3-oxocyclohexen-1-yl)benzohydrazide (5) and arylmethylene nitriles 2a-c and 2d,e, respactively.Reacting 2-oxo-3H-indol-3-ylidene malonic acid derivatives 3a,b with 5 afforded dioxospiro [3H-indole-3,4ʹ-quinoline]-3ʹ-carbonitrile (15) and 2- oxo-[1H] indol-3-ylcyanoacetate (17), respactively.Treating 5 with the enaminoester 18 gave hexahydro-7,7-dimethyl-2,5-dioxoquinolin-3-yl]benzamide (20). Coupling of 5 with the aryl diazonium salts and heteroaryl diazonium salts gave the hydrazones (21) and tetrahydro-[1,2,4]triazolo[5,1-c] [1,2,4] benzotriazine-6-ylidene)benzohydrazide (26