RESUMEN
No direct evidence that genetically modified (GM) food may represent a possible danger for health has been reported so far; however, the scientific literature in this field is still quite poor. Therefore, we carried out an ultrastructural morphometrical and immunocytochemical study on hepatocytes from mice fed on GM soybean, in order to investigate eventual modifications of nuclear components of these cells involved in multiple metabolic pathways related to food processing. Our observations demonstrate significant modifications of some nuclear features in GM-fed mice. In particular, GM fed-mice show irregularly shaped nuclei, which generally represents an index of high metabolic rate, and a higher number of nuclear pores, suggestive of intense molecular trafficking. Moreover, the roundish nucleoli of control animals change in more irregular nucleoli with numerous small fibrillar centres and abundant dense fibrillar component in GM-fed mice, modifications typical of increased metabolic rate. Accordingly, nucleoplasmic (snRNPs and SC-35) and nucleolar (fibrillarin) splicing factors are more abundant in hepatocyte nuclei of GM-fed than in control mice. In conclusion, our data suggest that GM soybean intake can influence hepatocyte nuclear features in young and adult mice; however, the mechanisms responsible for such alterations remain unknown.
Asunto(s)
Alimentos Modificados Genéticamente , Glycine max , Hepatocitos/enzimología , Envejecimiento , Alanina Transaminasa/metabolismo , Alanina Transaminasa/ultraestructura , Animales , Aspartato Aminotransferasas/metabolismo , Aspartato Aminotransferasas/ultraestructura , Peso Corporal , Nucléolo Celular/ultraestructura , Núcleo Celular/enzimología , Núcleo Celular/metabolismo , Núcleo Celular/ultraestructura , Proteínas Cromosómicas no Histona/metabolismo , Retículo Endoplásmico Rugoso/ultraestructura , Femenino , Aparato de Golgi/ultraestructura , Hepatocitos/ultraestructura , Inmunohistoquímica , Ratones , Membrana Nuclear/ultraestructura , Poro Nuclear/ultraestructura , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Vesículas Secretoras/ultraestructuraRESUMEN
The pharmacokinetics of moricizine and two of its metabolites, moricizine sulfoxide and phenothiazine-2-carbamic acid ethyl ester sulfoxide, were studied in healthy control subjects and in patients with chronic liver disease (cirrhosis). Moricizine disposition was significantly altered by hepatic cirrhosis. Compared to healthy subjects, the hepatic disease patients had an increased Cmax (59%), an increased t1/2 (141%), and a reduced plasma clearance (71%). Additionally, small but statistically significant increases were observed for tmax and the fraction of moricizine not bound to plasma proteins in patients with hepatic disease. The elimination of both moricizine metabolites was also altered by hepatic dysfunction as indicated by significantly prolonged terminal half-lives. Furthermore, there was a reduction in the conversion of moricizine to moricizine sulfoxide. Both hepatic blood flow and hepatic metabolizing capacity were assessed in all subjects and patients by administration of indocyanine green and antipyrine, respectively. Indocyanine green and antipyrine plasma clearances were decreased by 38 and 51%, respectively, indicating that both functions were diminished by hepatic cirrhosis. We conclude that the moricizine dose required for arrhythmia patients with hepatic disease should be lower, and perhaps, the dosing frequency should be less than in patients with normal liver function.