RESUMEN
To investigate the modifying effect of enzymatically modified isoquercitrin (EMIQ) on hepatocellular tumor promotion induced by beta-naphthoflavone (BNF) treatment, male rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) and were fed a diet containing BNF (0.5%) for 6 weeks with or without EMIQ (0.2%) in the drinking water after DEN initiation. One week after the commencement of the administration of BNF, rats were subjected to a two-thirds partial hepatectomy. The number and area of GST-P positive foci, the number of COX2-positive cells and the area of elastica-van Gieson (EVG)-positive connective tissue fibers promoted by BNF were significantly suppressed by the administration of the antioxidant EMIQ. Real-time RT-PCR analysis revealed that EMIQ treatment decreased mRNA expression levels of Gstm1, Serpine1, Cox2 and Nfkbia and increased mRNA expression levels of Yc2 compared with those in the DEN-BNF group. These results suggest that co-administration of EMIQ suppresses the hepatocellular tumor-promoting activity of BNF in rats through the anti-inflammatory effects of EMIQ and restores the cellular redox balance altered by BNF.
Asunto(s)
Anticarcinógenos , Antioxidantes/química , Antioxidantes/farmacología , Lesiones Precancerosas/prevención & control , Quercetina/análogos & derivados , beta-naftoflavona/antagonistas & inhibidores , beta-naftoflavona/toxicidad , Animales , Tejido Conectivo/efectos de los fármacos , Tejido Conectivo/metabolismo , Ciclooxigenasa 2/metabolismo , Glutatión Peroxidasa/metabolismo , Inmunohistoquímica , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/patología , Masculino , Lesiones Precancerosas/patología , Quercetina/química , Quercetina/farmacología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Endogámicas F344 , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Gill and kidney DNA integrity (alkaline unwinding assay) was assessed in Anguilla anguilla exposed for 24-h to copper (Cu: 1 or 2.5 µM), with or without 24-h pre-exposure to a polycyclic aromatic hydrocarbon (PAH)-like compound--ß-naphthoflavone (BNF: 2.7 µM). Gill showed DNA integrity loss in all the exposure conditions, reflecting a dual mode of BNF-Cu interaction depending on the metal concentration. Thus, antagonistic or additive effects were observed for BNF+Cu 1 µM or BNF+Cu 2.5 µM, respectively. Kidney showed decreased DNA integrity for single exposures (BNF, Cu 1 µM), whereas sequential exposures displayed higher DNA integrity than BNF alone, revealing a Cu antagonistic effect at both the concentrations. The results also demonstrated that (i) both organs are receptive for Cu inhibitory role against BNF genotoxicity; (ii) kidney is more resistant to Cu individual exposures; and (iii) under multi-pollution conditions genotoxicity cannot be predicted on the basis of individual chemicals responses.
Asunto(s)
Anguilla/fisiología , Cobre/toxicidad , Contaminantes Químicos del Agua/toxicidad , beta-naftoflavona/toxicidad , Anguilla/genética , Anguilla/metabolismo , Animales , Daño del ADN , Interacciones Farmacológicas , Inhibidores Enzimáticos/toxicidad , Branquias/efectos de los fármacos , Branquias/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Mutágenos/toxicidad , beta-naftoflavona/antagonistas & inhibidoresRESUMEN
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to increase plasma ACTH concentrations in male Sprague-Dawley rats and in male rat primary anterior pituitary cell cultures. The present study examined whether the anterior pituitary effects observed after TCDD exposure are mediated via the Ah receptor (AhR). Primary anterior pituitary cell cultures were prepared from normal 180- to 220-g male rats and the cultures treated with alpha-naphthoflavone (ANF), an antagonist; beta-naphthoflavone (BNF), an agonist; BNF + TCDD; 3,3',4,4',5-pentachlorobiphenyl (PCB), which is known to bind to the AhR; and 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), which does not bind the AhR. Support for the TCDD-AhR-mediated increases in ACTH concentrations is provided by the following observations: (1) ANF inhibited both the 1.3- to 2-fold TCDD-induced increase in basal medium and intracellular ACTH concentrations and the 30% TCDD-induced decrease in medium ACTH levels and the 1.2-fold increase in intracellular ACTH levels in corticotropin-releasing hormone (CRH)-stimulated cells, (2) BNF increased basal medium (1.7-fold) and intracellular (1.3-fold) ACTH concentrations, (3) BNF + TCDD demonstrated additivity by increasing basal medium (2.4-fold) and intracellular (1.7-fold) ACTH concentrations, (4) PCB increased basal medium (1.8- to 2.1-fold) and intracellular (1.3- to 1.8-fold) ACTH concentrations and inhibited medium ACTH secretion in CRH stimulated cells by 24-43%, and (5) HCB did not effect basal or CRH stimulated medium and intracellular ACTH concentrations. From this study it appears that TCDD-induced changes in ACTH secretion and synthesis by cultured anterior pituitary cells is mediated through the Ah receptor.