title: Reduced graphene oxide: nanotoxicological profile in rats.
abstract: BACKGROUND
  We have previously demonstrated that reduced graphene oxide (rGO) administered intravenously in rats was detected inside the hippocampus after downregulation of the tight and adherens junction proteins of the blood-brain barrier. While down-regulators of junctional proteins could be useful tools for drug delivery through the paracellular pathway, concerns over toxicity must be investigated before clinical application. Herein, our purpose was to trace whether the rGO inside the hippocampus triggered toxic alterations in this brain region and in target organs (blood, liver and kidney) of rats at various time points (15 min, 1, 3 h and 7 days).
  
  
  RESULTS
  The assessed rGO-treated rats (7 mg/kg) were clinically indistinguishable from controls at all the time points. Hematological, histopathological (neurons and astrocytes markers), biochemical (nephrotoxicity and hepatotoxicity assessment) and genotoxicological based tests showed that systemic rGO single injection seemed to produce minimal toxicological effects at the time points assessed. Relative to control, the only change was a decrease in the blood urea nitrogen level 3 h post-treatment and increases in superoxide dismutase activity 1 h and 7 days post-treatment. While no alteration in leukocyte parameters was detected between control and rGO-treated animals, time-dependent leukocytosis (rGO-1 h versus rGO-3 h) and leukopenia (rGO-3 h versus rGO-7 days) was observed intra-treated groups. Nevertheless, no inflammatory response was induced in serum and hippocampus at any time.
  
  
  CONCLUSIONS
  The toxic effects seemed to be peripheral and transitory in the short-term analysis after systemic administration of rGO. The effects were self-limited and non-significant even at 7 days post-rGO administration.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, 13083-881, Brazil. monique.cpm@gmail.com.|Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil. monique.cpm@gmail.com.
authors.forename: Monique Culturato Padilha
authors.initials: MC
authors.lastname: Mendonça
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Edilene Siqueira
authors.initials: ES
authors.lastname: Soares
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Marcelo Bispo
authors.initials: MB
authors.lastname: de Jesus
authors.affiliation: Department of Semiconductors, Instruments and Photonics, School of Electrical and Computer Engineering, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Helder José
authors.initials: HJ
authors.lastname: Ceragioli
authors.affiliation: Faculty of Technology of Sorocaba, State Center of Paula Souza Technological Education, Sorocaba, SP, Brazil.
authors.forename: Silvia Pierre
authors.initials: SP
authors.lastname: Irazusta
authors.affiliation: Department of Food and Nutrition, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Ângela Giovana
authors.initials: ÂG
authors.lastname: Batista
authors.affiliation: Department of Genetics, Evolution and Bioagents, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Marco Aurélio Ramirez
authors.initials: MA
authors.lastname: Vinolo
authors.affiliation: Department of Food and Nutrition, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Mário Roberto
authors.initials: MR
authors.lastname: Maróstica Júnior
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, 13083-881, Brazil. hofling@unicamp.br.|Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil. hofling@unicamp.br.
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz-Höfling
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000648:ultrastructure; D001806:Blood Urea Nitrogen; D004334:Drug Administration Schedule; D004909:Erythrocyte Indices; D006108:Graphite / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000648:ultrastructure; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000648:ultrastructure; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010087:Oxides; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D018675:Toxicity Tests
chemical_list: D010087:Oxides; D006108:Graphite; D013482:Superoxide Dismutase
keywords: Blood–brain barrier; Nanoparticles; Toxicity