RESUMO
The choroid plexus (CP) is rich in barrier mechanisms including transporters and enzymes which can influence drug disposition between blood and brain. We have limited knowledge of their state in fetus. We have studied barrier mechanisms along with metabolism and transporters influencing xenobiotics, using RNAseq and protein analysis, in the CP during the second-half of gestation in a nonhuman primate (Papio hamadryas). There were no differences in the expression of the tight-junctions at the CP suggesting a well-formed fetal blood-CSF barrier during this period of gestation. Further, the fetal CP express many enzymes for phase I-III metabolisms as well as transporters suggesting that it can greatly influence drug disposition and has a significant machinery to deactivate reactive molecules with only minor gestational changes. In summary, the study suggests that from, at least, midgestation, the CP in the nonhuman primate is restrictive and express most known genes associated with barrier function and transport.
Assuntos
Barreira Hematoencefálica/metabolismo , Plexo Corióideo/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Papio hamadryas/metabolismo , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Xenobióticos/metabolismo , Animais , Antioxidantes/metabolismo , Biotransformação , Barreira Hematoencefálica/crescimento & desenvolvimento , Plexo Corióideo/crescimento & desenvolvimento , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Proteínas de Membrana Transportadoras/genética , Modelos Animais , Papio hamadryas/genética , Papio hamadryas/crescimento & desenvolvimento , Gravidez , Proteínas de Junções Íntimas/genética , Distribuição Tecidual , Xenobióticos/líquido cefalorraquidiano , Xenobióticos/farmacocinéticaRESUMO
A direct in-line pre-column extraction technique in which guanidinium and ammonium sulfate are used, followed by column switching, was employed to analyze serum, plasma and cerebrospinal fluid samples of patients treated for tuberculous meningitis. Resolution of a wide range of polar to non-polar xenobiotics was obtained on a C8 silica column by using a linear gradient from a binary system consisting of solvent A (0.05 M KH2PO4) and solvent B (acetonitrile-isopropanol, 4:1, v/v). Apart from the antituberculosis drugs (isoniazid, pyrazinamide, ethionamide and rifampicin) the patients received up to sixteen different medicines for prevention of complications and the treatment of symptoms. Qualitative resolution of all the drugs was obtained by the chromatographic system. Quantitation of pyrazinamide and ethionamide was achieved with high precision and low inter-sample variation.
