title: Protective effect of meloxicam-loaded nanocapsules against amyloid-β peptide-induced damage in mice.
abstract: The objective of present study was to investigate the protective effect of M-NC against aβ (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) aβ, (III) M-NC, (IV) M-F, (V) M-NC+aβ and (VI) M-F+aβ. Mice were pre-treated with M-NC (5mg/kg, by gavage), M-F (5mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, aβ peptide (3nmol) or filtered water were i.c.v. injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that aβ peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aβ peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aβ peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aβ peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by aβ peptide.
authors.affiliation: Mestrado em Nanociências, Centro de Ciências Tecnológicas, Centro Universitário Franciscano, Santa Maria, CEP 97010-032, RS, Brazil.
authors.forename: Francine R
authors.initials: FR
authors.lastname: Ianiski
authors.forename: Catiane B
authors.initials: CB
authors.lastname: Alves
authors.forename: Ana Cristina G
authors.initials: AC
authors.lastname: Souza
authors.forename: Simone
authors.initials: S
authors.lastname: Pinton
authors.forename: Silvane S
authors.initials: SS
authors.lastname: Roman
authors.forename: Cristiano R B
authors.initials: CR
authors.lastname: Rhoden
authors.forename: Marta P
authors.initials: MP
authors.lastname: Alves
authors.forename: Cristiane
authors.initials: C
authors.lastname: Luchese
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D000077239:Meloxicam; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D053769:Nanocapsules / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053769:Nanocapsules; D010446:Peptide Fragments; D013843:Thiazines; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); C108078:catalase I; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D000077239:Meloxicam