RESUMO
Various NMDA-receptor antagonists have been investigated for their therapeutic potential in Alzheimer's disease with memantine shown to be safe and with relative efficacy. There is, however, need to develop novel drugs to counter tolerance and with better efficacy in ameliorating neurodegeneration. We have shown neurodegeneration in different models of vanadium-exposed mice. This study was designed to evaluate and ascertain the potency of three novel NMDA-receptor antagonists (Compounds A, B and C) to ameliorate neurodegeneration in vanadium-exposed mice. One-month-old mice (n = 6) received sterile water (control) and another group (n = 6) was treated with vanadium (3 mg/kg sodium metavanadate) intraperitoneally for 1 month. Three other groups (n = 6) received vanadium and compounds A, B and C (4.35 mg/kg, 30 mg/kg and 100 mg/kg, respectively) simultaneously for the same period. Assessment of pathologies and neurodegeneration in different brain regions was done to test the ameliorative effects of the 3 antagonists using different immunohistochemical markers. Vanadium exposure resulted in reduced calbindin expression and pyknosis of Purkinje cells, cell loss and destruction of apical dendrites with greater percentage of cytoplasmic vacuolations, morphological alterations characterized by cell clustering and multiple layering patterns in the Purkinje cell layer. In addition, the observed degeneration included demyelination, increased GFAP-immunoreactive cells and microgliosis. Simultaneous administration of the compounds to vanadium-exposed mice resulted in the preservation of cellular integrity in the same anatomical regions and restoration of the cells' vitality with reduced astroglial and microglial activation.
Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Degeneração Neural , Síndromes Neurotóxicas/prevenção & controle , Células de Purkinje/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Calbindinas/metabolismo , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Células de Purkinje/metabolismo , Células de Purkinje/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , VanadatosRESUMO
Dependence between therapeutic dose and activity induced in mammal bones is discussed. This activity leads to gamma ray emission registered by HPGe detector and scintilation probe. Presented results are focused on activation which occurs during emission of 15 and 20 MV photon beams. The purpose is to describe how therapeutic conditions (dose, time of irradiation) influence the induced radioactivity. Preliminary studies of decay rate, calculation of half-life and identification of isotopes involved in this dynamic process are given.
