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Genotoxic, neurotoxic and neuroprotective activities of apomorphine and its oxidized derivative 8-oxo-apomorphine
Picada, J. N; Roesler, R; Henriques, J. A. P.
  • Picada, J. N; Universidade Luterana do Brasil. Canoas. BR
  • Roesler, R; Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Farmacologia. Porto Alegre. BR
  • Henriques, J. A. P; Universidade Luterana do Brasil. Canoas. BR
Braz. j. med. biol. res ; 38(4): 477-486, Apr. 2005. tab
Artículo en Inglés | LILACS | ID: lil-398187
ABSTRACT
Apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent in the treatment of patients with Parkinson's disease. Both in vivo and in vitro studies have shown that apomorphine displays both antioxidant and pro-oxidant actions, and might have either neuroprotective or neurotoxic effects on the central nervous system. Some of the neurotoxic effects of apomorphine are mediated by its oxidation derivatives. In the present review, we discuss recent studies from our laboratory in which the molecular, cellular and neurobehavioral effects of apomorphine and its oxidized derivative, 8-oxo-apomorphine-semiquinone (8-OASQ), were evaluated in different experimental models, i.e., in vitro genotoxicity in Salmonella/microsome assay and WP2 Mutoxitest, sensitivity assay in Saccharomyces cerevisiae, neurobehavioral procedures (inhibition avoidance task, open field behavior, and habituation) in rats, stereotyped behavior in mice, and Comet assay and oxidative stress analyses in mouse brain. Our results show that apomorphine and 8-OASQ induce differential mutagenic, neurochemical and neurobehavioral effects. 8-OASQ displays cytotoxic effects and oxidative and frameshift mutagenic activities, while apomorphine shows antimutagenic and antioxidant effects in vitro. 8-OASQ induces a significant increase of DNA damage in mouse brain tissue. Both apomorphine and 8-OASQ impair memory for aversive training in rats, although the two drugs showed a different dose-response pattern. 8-OASQ fails to induce stereotyped behaviors in mice. The implications of these findings are discussed in the light of evidence from studies by other groups. We propose that the neuroprotective and neurotoxic effects of dopamine agonists might be mediated, in part, by their oxidized metabolites.
Asunto(s)
Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Quinonas / Conducta Animal / Apomorfina / Agonistas de Dopamina / Antiparkinsonianos Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Inglés Revista: Braz. j. med. biol. res Asunto de la revista: Biologia / Medicina Año: 2005 Tipo del documento: Artículo / Congreso y conferencia País de afiliación: Brasil Institución/País de afiliación: Universidade Federal do Rio Grande do Sul/BR / Universidade Luterana do Brasil/BR

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Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Quinonas / Conducta Animal / Apomorfina / Agonistas de Dopamina / Antiparkinsonianos Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Inglés Revista: Braz. j. med. biol. res Asunto de la revista: Biologia / Medicina Año: 2005 Tipo del documento: Artículo / Congreso y conferencia País de afiliación: Brasil Institución/País de afiliación: Universidade Federal do Rio Grande do Sul/BR / Universidade Luterana do Brasil/BR