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Mar Pollut Bull ; 142: 54-57, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31232336


Plastic debris in the oceans is a major and growing problem in global environmental pollution. There are increasing concerns that plastic debris is a source of contaminant, either added during manufacturing or adsorbed from the environment. However, there is little information about the acute toxicity of leachates from plastic debris on marine organisms. In this study, we conducted experiments to evaluate the toxicity of leachates from two single-use polyethylene plastic bags (PB1 and PB2) with the embryo and larvae of the commercial clam Meretrix meretrix. Results showed that fertilization of the embryos was not affected by plastic leachates, but the developments of D-veliger larvae, including survival, deformity, and shell height, were significantly affected by plastic leachates from both PB1 and PB2 compared to the controls of filtered seawater. We speculate that compounds leaching from plastic bags are responsible for the observed toxicity. Therefore, leaching toxicity from plastic debris should be considered when assessing the risks of plastic pollution in the oceans.

Bivalves/efeitos dos fármacos , Polietileno/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bivalves/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Alimentos Marinhos , Água do Mar
Chin J Nat Med ; 13(7): 540-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26233845


The present study was designed to investigate the effects of Laminaria japonica (Laminaria) on pharmacokinetics of glycyrrhetinic acid (GA) following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid (GL). The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter Tmax. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.

Interações de Medicamentos , Ácido Glicirretínico/sangue , Glycyrrhiza/química , Ácido Glicirrízico/farmacocinética , Absorção Intestinal , Laminaria , Extratos Vegetais/farmacologia , Administração Oral , Animais , Ácido Glicirrízico/sangue , Mucosa Intestinal/metabolismo , Masculino , Extratos Vegetais/sangue , Extratos Vegetais/farmacocinética , Ratos Sprague-Dawley
J Pharmacol Sci ; 124(4): 468-79, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24739264


Clozapine (CLZ) was reported to be associated with hepatotoxicity. Glycyrrhetinic acid (GA) has a liver protective effect. Our preliminary experiments showed that GA aggravated rather than attenuated CLZ-induced hepatotoxicity in primary cultured rat hepatocytes. The study aimed to describe the enhancing effect of GA on CLZ-induced hepatotoxicity in vivo and in vitro. Data from primary cultured rat hepatocytes showed the decreased formation of metabolites demethylclozapine (nor-CLZ) and clozapine N-oxide (CLZ N-oxide). The results in vivo showed that 7-day CLZ treatment led to marked accumulation of triglyceride (TG) and increase in γ-glutamyl transpeptidase (γ-GT) activity, liver weight, and serum AST in rats. Co-administration of GA enhanced the increases in hepatic TG, γ-GT, liver weight, and serum total cholesterol induced by CLZ. GA decreased plasma concentrations of nor-CLZ and CLZ N-oxide. Compared with control rats, hepatic microsomes of GA rats exhibited the decreased formations of nor-CLZ and CLZ N-oxide, accompanied by decreases in activities of CYP2C11 and CYP2C19 and increased activity of CYP1A2. QT-PCR analysis demonstrated that GA enhanced expression of CYP1A2, but suppressed expression of CYP2C11 and CYP2C13. All these results support the conclusion that GA aggravated CLZ-induced hepatotoxicity, which was partly via inhibiting CYP2C11 and CYP2C13 or inducing CYP1A2.

Antipsicóticos/toxicidade , Clozapina/toxicidade , Ácido Glicirretínico/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Animais , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Hidrocarboneto de Aril Hidroxilases/metabolismo , Células Cultivadas , Colesterol/sangue , Clozapina/análogos & derivados , Clozapina/metabolismo , Citocromo P-450 CYP1A2 , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/metabolismo , Família 2 do Citocromo P450 , Citocromos/metabolismo , Sinergismo Farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Esteroide 16-alfa-Hidroxilase/antagonistas & inibidores , Esteroide 16-alfa-Hidroxilase/metabolismo , Triglicerídeos/metabolismo , gama-Glutamiltransferase/metabolismo