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dc.contributor.authorPicada, Jaqueline Nascimentopt_BR
dc.contributor.authorRoesler, Rafaelpt_BR
dc.contributor.authorHenriques, João Antonio Pêgaspt_BR
dc.date.accessioned2010-04-24T04:15:40Zpt_BR
dc.date.issued2005pt_BR
dc.identifier.issn0100-879Xpt_BR
dc.identifier.urihttp://hdl.handle.net/10183/21192pt_BR
dc.description.abstractApomorphine 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.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofBrazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas. Ribeirão Preto, SP. Vol. 38, no. 4 (Apr. 2005), p. 477-486pt_BR
dc.rightsOpen Accessen
dc.subjectBioquímicapt_BR
dc.subjectApomorphineen
dc.subject8-Oxo-apomorphinesemiquinoneen
dc.subjectDopamineen
dc.subjectGenotoxicityen
dc.subjectNeurotoxicityen
dc.titleGenotoxic, neurotoxic and neuroprotective activities of apomorphine and its oxidized derivative 8-oxo-apomorphinept_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb000524143pt_BR
dc.type.originNacionalpt_BR


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