title: Effects of cholinergic stimulation with pyridostigmine bromide on chronic chagasic cardiomyopathic mice.
abstract: The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido), on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con) or chronically infected (5 months) with Trypanosoma cruzi (chagasic:Chg) were treated or not (NT) with Pyrido for one month. At the end of this period, electrocardiogram (ECG); cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFNγ with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice.
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Marília Beatriz
authors.initials: MB
authors.lastname: de Cuba
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Marcus Paulo Ribeiro
authors.initials: MP
authors.lastname: Machado
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Thais Soares
authors.initials: TS
authors.lastname: Farnesi
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Angelica Cristina
authors.initials: AC
authors.lastname: Alves
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Livia Alves
authors.initials: LA
authors.lastname: Martins
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Lucas Felipe
authors.initials: LF
authors.lastname: de Oliveira
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Caroline Santos
authors.initials: CS
authors.lastname: Capitelli
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Camila Ferreira
authors.initials: CF
authors.lastname: Leite
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Marcos Vinícius
authors.initials: MV
authors.lastname: Silva
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Juliana Reis
authors.initials: JR
authors.lastname: Machado
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Henrique Borges
authors.initials: HB
authors.lastname: Kappel
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Helioswilton Sales
authors.initials: HS
authors.lastname: de Campos
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Paiva
authors.affiliation: Oswaldo Cruz Institute, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Natália Lins da Silva
authors.initials: NL
authors.lastname: Gomes
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Ana Carolina Guimarães
authors.initials: AC
authors.lastname: Faleiros
authors.affiliation: Oswaldo Cruz Institute, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Constança Felicia de Paoli de Carvalho
authors.initials: CF
authors.lastname: Britto
authors.affiliation: Oswaldo Cruz Institute, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.affiliation: Oswaldo Cruz Institute, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Otacílio Cruz
authors.initials: OC
authors.lastname: Moreira
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Virmondes
authors.initials: V
authors.lastname: Rodrigues
authors.affiliation: Department of Clinical Sciences, Internal Medicine II, L. Sacco Hospital, University of Milan, 20157 Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Montano
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Eliane
authors.initials: E
authors.lastname: Lages-Silva
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Ramirez
authors.affiliation: Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Valdo Jose Dias
authors.initials: VJ
authors.lastname: da Silva
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism; D014355:Chagas Disease / Q000188:drug therapy* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D002908:Chronic Disease / Q000188:drug therapy*; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011729:Pyridostigmine Bromide / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000472:pathogenicity
chemical_list: D002800:Cholinesterase Inhibitors; D007371:Interferon-gamma; D011729:Pyridostigmine Bromide