RESUMO
The protective effect of the supplementation with an aqueous-ethanolic extract obtained from Ulva lactuca (Delile) green seaweed on benzo[a] pyrene-induced damage in mice was evaluated. Animals were treated with oral doses of U. lactuca extract (100 and 400 mg/kg) for 9 weeks. They were exposed to 50 mg/kg of oral doses of benzo(a)pyrene starting from the second week and up to the fifth week. Groups treated with benzo(a)pyrene only (second to fifth weeks), sunflower oil (vehicle, 9 weeks), or U. lactuca extract (100 and 400 mg/kg, 9 weeks) were also included in the study. The treatment with 400 mg/kg of the extract ameliorated the oxidative damage, decreased IL-1ß and TNF-α levels, and favorably regulated the antioxidant defenses compared with benzo(a)pyrene-exposed group. The benzo(a)pyrene-induced DNA damage was also reduced, as it was evidenced by the lower micronucleus formation in U. lactuca extract-supplemented animals. The extract protected the hepatic tissue, and it reduced the liver activity/expression of CYP1A1. These results altogether suggested a chemoprotective effect of U. lactuca extract against benzo(a)pyrene-induced-toxicity in mice, probably associated with an inhibitory effect of carcinogen bioactivation.
Assuntos
Citocromo P-450 CYP1A1/antagonistas & inibidores , Alga Marinha , Ulva , Animais , Benzo(a)pireno/toxicidade , Suplementos Nutricionais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The aqueous stem bark extract of Mangifera indica L. (MSBE) has been reported to have antioxidant, anti-inflammatory and analgesic properties. In previous studies, we showed that MSBE and mangiferin, its main component, lower the activity of some cytochrome P-450 (P450) enzymes in rat hepatocytes and human liver microsomes. In the present study, the effects of MSBE and mangiferin on several P450 enzymes and UDP-glucuronosyltransferases (UGTs) in human-cultured hepatocytes have been examined. After hepatocytes underwent a 48-h treatment with sub-cytotoxic concentrations of the products (50-250 µg/mL), a concentration-dependent decrease of the activity of the five P450 enzymes measured (CYP1A2, 2A6, 2C9, 2D6 and 3A4) was observed. For all the activities, a reduction of at least 50% at the highest concentration (250 µg/mL) was observed. In addition, UGT activities diminished. MSBE considerably reduced UGT1A9 activity (about 60% at 250 µg/mL) and lesser effects on the other UGTs. In contrast, 250 µg/mL mangiferin had greater effects on UGT1A1 and 2B7 than on UGT1A9 (about 55% vs. 35% reduction, respectively). Quantification of specific mRNAs revealed reduced CYP3A4 and 3A5 mRNAs content, and an increase in CYP1A1, CYP1A2, UGT1A1 and UGT1A9 mRNAs. No remarkable effects on the CYP2A6, 2B6, 2C9, 2C19, 2D6 and 2E1 levels were observed. Our results suggest that the activity and/or expression of major P450 and UGT enzymes is modulated by MSBE and that potential herb-drugs interactions could arise after a combined intake of this extract with conventional medicines. Therefore, the potential safety risks of this natural product derived by altering the ADMET properties of co-administered drugs should be examined.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/metabolismo , Hepatócitos/efeitos dos fármacos , Mangifera/química , Extratos Vegetais/farmacologia , Células Cultivadas , Hepatócitos/enzimologia , Humanos , Casca de Planta/químicaRESUMO
We present a transversal alternating field electrophoresis chamber that allows modifiable inner widths to accommodate low- or high-throughput formats, with 7.8 cm opposite electrode separation and 30.4 cm electrode length. Removable slotted sheets divide the chamber into four smaller compartments, each one supporting a minigel of 3.85 cm in length and 7.1 cm in width. Replacements of slotted sheets with solid dielectric blocks with the sizes and shapes of compartments permit to occlude chamber compartments, changing from 4 to 1 the numbers of minigels per run, from 88 to 13 the maximum numbers of samples, and from 1688 to 422 mL the volume of buffer poured into the chamber. Saccharomyces cerevisiae chromosomes gave its characteristic DNA band pattern in all compartments, whereas migrations of DNA molecules are not affected by the occlusion of compartments.