RESUMO
AIM: To detect the effect of tetrandrine (Tet) on c-fos gene expression in cerebrum induced by lindane, a neurotoxicant which activates Ca2+ channels. METHODS: Northern and dot blotting, dual wavelength thin layer chromatography scanner, were used in this study. RESULTS: Lindane 30 mg.kg-1 given by intragastric gavage (i.g.) increased the expression of c-fos gene to 146 mm2 in rat cerebrum 1 h after treatment. Tet 1, 2, and 4 mg.kg-1 given by i.g. 30 min prior to lindane reduced c-fos gene expression in a concentration-dependent manner. Expressed genes reached only 86, 40, and 39 mm2, respectively. CONCLUSION: Tet inhibited c-fos gene expression in rat cerebrum induced by Ca2+ agonist-lindane.
Assuntos
Alcaloides/farmacologia , Benzilisoquinolinas , Encéfalo/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Genes fos , Animais , Expressão Gênica , Hexaclorocicloexano/antagonistas & inibidores , Masculino , RNA Mensageiro/genética , Ratos , Ratos WistarRESUMO
The ability of tetrandrine (Tet), as a Ca2+ antagonist isolated from a traditional Chinese herb, to reduce cortical neuronal injury was quantitatively examined in cell cultures derived from fetal rats by measurement of lactate dehydrogenase (LDH) released to the extracellular bathing media. Cell cultures exposed to excitotoxins-glutamate (Glu), N-methyl-D-aspartate (NMDA), beta-N-oxalylamino-L-alanine(BOAA, on non-NMDA receptors) and beta-N-methylamino-L-alanine(BMAA, on NMDA receptors)-for 24 h showed widespread neuronal injury, which was substantially attenuated by addition of Tet 10(-7)-10(-6) mol.L-1 except to NMDA. Tet failed to protect neurons against NMDA. These results suggest that Tet has protective effect on fetal rat cortical neuronal injury induced by some excitotoxins in vitro. The mechanism of action was hypothesized that opening of Ca2+ channel in cellular membrane would not happen, because of inhibition of Na+ influx and membrane depolarization induced by Tet. As a result, cytosolic free Ca2+ overload and then neuroal injury were prevented or lightened.
Assuntos
Alcaloides/farmacologia , Benzilisoquinolinas , Bloqueadores dos Canais de Cálcio/farmacologia , Córtex Cerebral/patologia , Neurotoxinas/antagonistas & inibidores , Diamino Aminoácidos/antagonistas & inibidores , Animais , Células Cultivadas , Córtex Cerebral/metabolismo , Toxinas de Cianobactérias , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feto , L-Lactato Desidrogenase/metabolismo , N-Metilaspartato/antagonistas & inibidores , Neurônios/patologia , Ratos , Ratos Wistar , beta-Alanina/análogos & derivados , beta-Alanina/antagonistas & inibidoresRESUMO
Cytosolic free Ca(2+)-[Ca2+]i was measured in dissociated cerebral cells isolated from fetal rats using the fluorescent indicator Fura-2. Increases in [Ca2+]i occurred rapidly following exposure of the cells to 50 mmol.L-1 KCl, 10(-7) mol.L-1 Bay K 8644 and 200 mumol.L-1 glutamate (Glu). [Ca2+]i elevation produced by K(+)-depolarization was blocked completely by pretreatment with tetrandrine (Tet) of various concentrations (10(-9) - 10(-7) mol.L-1, final). Tet showed significant inhibitory effect on [Ca2+]i increases stimulated by Glu in concentration-dependent manner. With Tet 10(-7) mol.L-1, Bay K 8644-induced increases in [Ca2+]i were reduced markedly. These results indicate that Tet can block the increases in [Ca2+]i in fetal rat cerebral cells induced by Ca2+ agonists, suggesting that this drug may have a protective effect on cerebral cell injury.
