RESUMO
Ex vivo perfusion of the human term placenta is a method to study placental transfer without extrapolation from animal to human and with no ethical concerns for mother and child. However, ex vivo placenta perfusion has a limited potential within chemical screening and testing as the method is time-consuming. This study was an attempt to construct data needed to develop quantitative structure-activity relationship (QSAR) models that are able to predict placental transfer of new compounds. Placental transfer is a biological activity that statistically may be related to the physiochemical properties of a given group of compounds. Benzoic acid, caffeine, and glyphosate were chosen as model compounds because they are small molecules with large differences in physiochemical properties. Caffeine crossed the placenta by passive diffusion. The initial transfer rate of benzoic acid was more limited in the first part of the perfusion compared to caffeine, but reached the same steady-state level by the end of perfusion. The transfer of glyphosate was restricted throughout perfusion, with a lower permeation rate, and only around 15% glyphosate in maternal circulation crossed to the fetal circulation during the study period.
Assuntos
Ácido Benzoico/metabolismo , Cafeína/metabolismo , Glicina/análogos & derivados , Troca Materno-Fetal/fisiologia , Placenta/metabolismo , Adulto , Ácido Benzoico/química , Cafeína/química , Feminino , Glicina/química , Glicina/metabolismo , Humanos , Técnicas In Vitro , Modelos Biológicos , Perfusão , Gravidez , Relação Quantitativa Estrutura-Atividade , GlifosatoRESUMO
The present study was undertaken in order to investigate if toluene induced oxidative stress in brains from rats exposed prenatally to 1800 ppm toluene 6 hr/day at days 7-20 during the pregnancy. 35-42 days after birth the rats were killed and synaptosomal fractions were prepared for the experiments. Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes than from unexposed. The membrane fluidity increased significantly when synaptosomes were incubated with toluene for 10 min. in vitro but the change in fluidity was identical in both groups of offspring. The results indicate that prenatal exposure to toluene induces long-lasting changes in oxidative status and membrane function.