title: Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.
abstract: Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the hippocampus.
authors.affiliation: Programa de Pós-graduação em Ciências Fisiológicas-Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Lidiane
authors.initials: L
authors.lastname: Dal Bosco
authors.affiliation: Programa de Pós-graduação em Ciências Fisiológicas-Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Gisele E
authors.initials: GE
authors.lastname: Weber
authors.affiliation: Programa de Pós-graduação em Ciências Fisiológicas-Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Gustavo M
authors.initials: GM
authors.lastname: Parfitt
authors.affiliation: Escola de Química e Alimentos, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Cordeiro
authors.affiliation: Instituto de Ciências Exatas, Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Sangram K
authors.initials: SK
authors.lastname: Sahoo
authors.affiliation: Instituto de Ciências Exatas, Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Fantini
authors.affiliation: Programa de Pós-graduação em Aquicultura, Instituto de Oceanografia, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Marta C
authors.initials: MC
authors.lastname: Klosterhoff
authors.affiliation: Programa de Pós-graduação em Aquicultura, Instituto de Oceanografia, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Romano
authors.affiliation: Laboratório de Química de Nanoestruturas, Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, MG, Brazil.
authors.forename: Clascídia A
authors.initials: CA
authors.lastname: Furtado
authors.affiliation: Laboratório de Química de Nanoestruturas, Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, MG, Brazil.
authors.forename: Adelina P
authors.initials: AP
authors.lastname: Santos
authors.affiliation: Programa de Pós-graduação em Ciências Fisiológicas-Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: José M
authors.initials: JM
authors.lastname: Monserrat
authors.affiliation: Programa de Pós-graduação em Ciências Fisiológicas-Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Barros
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001522:Behavior, Animal; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D037742:Nanotubes, Carbon / Q000737:chemistry; D018384:Oxidative Stress; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species
chemical_list: D000975:Antioxidants; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione