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dc.contributor.advisorWajner, Moacirpt_BR
dc.contributor.authorRibeiro, Rafael Teixeirapt_BR
dc.date.accessioned2021-03-04T04:16:40Zpt_BR
dc.date.issued2017pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/218404pt_BR
dc.description.abstractTissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L- 2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrarly administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2- HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in cerebral cortex and striatum of neonatal rats. L-2-HG markedly induced the generation of reactive oxygen species (increase of 2′,7′-dichloroflurescein-DCFH- oxidation), lipid peroxidation (increase of malondialdehyde concentrations) and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione - GSH) and sulfhydryl content in cerebral cortex. Alterations of the activities of various antioxidant enzymes were also observed in cerebral cortex and striatum following L-2-HG administration. Furthermore, L-2-HG-induced lipid peroxidation and GSH decrease in cerebral cortex were prevented by the antioxidant melatonin and by the classical antagonist of NMDA glutamate receptor MK-801, suggesting the involvement of reactive species and of overstimulation of NMDA receptor in these effects. Finally, L-2-HG provoked vacuolation and edema particularly in the cerebral cortex with less intense alterations in the striatum that were possibly associated with the unbalanced redox homeostasis caused by this metabolite. Taken together, it is presumed that these pathomechanisms may underlie the neurological symptoms and brain abnormalities observed in the affected patients.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.rightsOpen Accessen
dc.subjectL-2-hydroxyglutaric aciduriaen
dc.subjectFarmáciapt_BR
dc.subjectHistopathologyen
dc.subjectStriatumen
dc.subjectCerebral cortexen
dc.subjectRedox homeostasisen
dc.subjectL-2-hydroxyglutaric aciden
dc.titleExperimental evidence that in vivo intracerebral administration of L-2-hydroxyglutaric acid to neonatal rats provokes disruption of redox status and histopathological abnormalities in the brainpt_BR
dc.typeTrabalho de conclusão de graduaçãopt_BR
dc.identifier.nrb001066111pt_BR
dc.degree.grantorUniversidade Federal do Rio Grande do Sulpt_BR
dc.degree.departmentFaculdade de Farmáciapt_BR
dc.degree.localPorto Alegre, BR-RSpt_BR
dc.degree.date2017pt_BR
dc.degree.graduationFarmáciapt_BR
dc.degree.levelgraduaçãopt_BR


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