RESUMO
The developing nervous system is susceptible to lead (Pb) exposure but less is known about the effect of this toxic agent in adult rat brain. Since astrocytes serve as a cellular Pb deposition site, it is of importance to investigate the response of astroglial cells in the adult rat brain in a model of acute lead exposure (25 mg/kg b.w. of lead acetate, i.p. for 3 days). An increased immunoreactivity of glial fibrillary acidic protein (GFAP) on Western blots was noticeable in fractions of astroglial origin-glial plasmalemmal vesicles (GPV) and in homogenates from the hippocampus and cerebral cortex but not in the cerebellum. The features of enhanced astrocytic reactivity (i.e. large accumulation of mitochondria, activated Golgi apparatus and increment of gliofilaments) were observed in electron microscopy studies in the same tissues. Total glutathione levels increased both in GPV fractions and in brain homogenates-in the cerebellum (120% above control) and in hippocampus (30% above control). The results of current studies indicate that acute lead exposure is accompanied by astrocyte activation connected with the presence of the enhanced expression of GFAP. It may indicate lead-induced neuronal injury. At the same time, a regional enhancement of detoxicative mechanisms (GSH) was noticed, suggesting activation of astrocyte-mediated neuroprotection against toxic Pb action.
Assuntos
Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Intoxicação do Sistema Nervoso por Chumbo/patologia , Doença Aguda , Animais , Astrócitos/metabolismo , Western Blotting , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Glutationa/metabolismo , Inativação Metabólica , Intoxicação do Sistema Nervoso por Chumbo/metabolismo , Masculino , Microscopia Eletrônica , Compostos Organometálicos/sangue , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/toxicidade , Ratos , Ratos WistarRESUMO
An in vitro system composed of nicked pBR322 DNA and purified topoisomerase I was employed to study the efficiency of the topoisomerase I-driven single-strand to double-strand DNA breaks conversion. At 1.4 x 10(5) topoisomerase I activity units per mg DNA about 20% single-strand nicks were converted into double-strand breaks during 30 min due to topoisomerase I action. Camptothecin inhibited the conversion. The conversion was also inhibited when the relaxing activity of the used topoisomerase I was increased by phosphorylation of the enzyme with casein kinase 2. The presented data suggest that topoisomerase I may be involved in production of double-stranded breaks in irradiated cells and that this process positively depends on the amount of topoisomerase I but not on its phosphorylation state.
