RESUMO
Epilepsy is a neurological disorder treated with antiepileptic drugs (AEDs). Since AEDs are administered in women in childbearing age, it is critical to study if drugs are capable of inducing developmental toxicity. Along the bibliography available, there is no research comparing teratogenicity and anticonvulsant effect within the same study. In the present study, we evaluated the teratogenic and anticonvulsant effects of six different AEDs: carbamazepine, levetiracetam, lamotrigine, phenobarbital, phenytoin and valproic acid. Zebrafish was the selected animal model because of its small size, rapid external development and similar neurophysiology to mammals. Zebrafish embryo and larvae were exposed to AEDs. Embryo development was monitored by their hatching and morphology. In larvae, locomotor activity was measured as a parameter of neurotoxicity. Finally, anticonvulsant effect was determined after exposure to AEDs in zebrafish larvae treated with the proconvulsant drug pentylenetetrazole. Our results suggest that lamotrigine and phenytoin could be suitable non-teratogenic and efficient anticonvulsant options for epilepsy treatment.
Assuntos
Anticonvulsivantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Teratogênese/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Anticonvulsivantes/toxicidade , Avaliação Pré-Clínica de MedicamentosRESUMO
In recent years, the use of commercial nanoparticles in different industry and health fields has increased exponentially. However, the uncontrolled application of nanoparticles might present a potential risk to the environment and health. Toxicity of these nanoparticles is usually evaluated by a fast screening assay in zebrafish (Danio rerio). The use of this vertebrate animal model has grown due to its small size, great adaptability, high fertilization rate and fast external development of transparent embryos. In this review, we describe the toxicity of different micro- and nanoparticles (carbon nanotubes, dendrimers, emulsions, liposomes, metal nanoparticles, and solid lipid nanoparticles) associated to their biophysical properties using this model. The main biophysical properties studied are size, charge and surface potential due to their impact on the environment and health effects. The review also discusses the correlation of the effects of the different nanoparticles on zebrafish. Special focus is made on morphological abnormalities, altered development and abnormal behavior. The last part of the review debates changes that should be made in future directions in order to improve the use of the zebrafish model to assess nanotoxicity.
RESUMO
In a previous work, we found that liposome hydrophobicity could affect deoxyribonucleic acid (DNA) association efficiency. Now, we have focused on the possible correlation between liposome hydrophobicity and DNA conformation. DNA lyophilized with cationic vesicles with high hydrophobicity changes its conformation into a more condensed form, probably the C form. With noncharged vesicles, it changes its conformation from B to a partial A form. These results contribute to a better understanding of the interaction between DNA and lipids, suggesting there is direct relationship between hydrophobicity and DNA conformation changes: The higher the hydrophobicity factor, the more pronounced the changes in DNA form, to a more condensed form.
RESUMO
The stability of liposomal formulations is a key issue in drug delivery. Liposomes made of egg phosphatidylcholine (EPC), cholesterol (Chol), sphingomyelin (SM), and gangliosides (GM1 and GM type III) were incubated in different media to determine their stability. Mixtures containing GM1 or GM type III were found to be the most stable, and both showed similar stability trends in plasma at 37 degrees C. EPC/Chol was the most susceptible to lysis in plasma. In acid media (pH 2), the highest stability corresponded to EPC/Chol, whereas in bile and pancreatin, liposomes with GM1 and GM type III were more stable than those containing SM. This study suggests that among the formulations used as oral drug carriers, those containing GM1 and GM type III have higher possibilities of surviving through the gastrointestinal tract.