title: Ouabain Modulates Zymosan-Induced Peritonitis in Mice.
abstract: Ouabain, a potent inhibitor of the Na(+), K(+)-ATPase, was identified as an endogenous substance. Recently, ouabain was shown to affect various immunological processes. We have previously demonstrated the ability of ouabain to modulate inflammation, but little is known about the mechanisms involved. Thus, the aim of the present work is to evaluate the immune modulatory role of ouabain on zymosan-induced peritonitis in mice. Our results show that ouabain decreased plasma exudation (33%). After induction of inflammation, OUA treatment led to a 46% reduction in the total number of cells, as a reflex of a decrease of polymorphonuclear leukocytes, which does not appear to be due to cell death. Furthermore, OUA decreased TNF-α (57%) and IL-1β (58%) levels, without interfering with IL-6 and IL-10. Also, in vitro experiments show that ouabain did not affect endocytic capacity. Moreover, electrophoretic mobility shift assay (EMSA) shows that zymosan treatment increased (85%) NF-κB binding activity and that ouabain reduced (30%) NF-κB binding activity induced by zymosan. Therefore, our data suggest that ouabain modulated acute inflammatory response, reducing the number of cells and cytokines levels in the peritoneal cavity, as well as NFκB activation, suggesting a new mode of action of this substance.
authors.affiliation: Instituto de Ciências Biomédicas, Departamento de Farmacologia, Laboratório de Neurofarmacologia Molecular, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil.
authors.forename: Jacqueline Alves
authors.initials: JA
authors.lastname: Leite
authors.affiliation: Centro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil.
authors.forename: Anne Kaliery De Abreu
authors.initials: AK
authors.lastname: Alves
authors.affiliation: Centro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil.
authors.forename: José Guilherme Marques
authors.initials: JG
authors.lastname: Galvão
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Imunologia Tumoral, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana Pires
authors.initials: MP
authors.lastname: Teixeira
authors.affiliation: Centro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil.
authors.forename: Luiz Henrique Agra
authors.identifier: 0000-0002-8445-5189
authors.initials: LH
authors.lastname: Cavalcante-Silva
authors.affiliation: Instituto de Ciências Biomédicas, Departamento de Farmacologia, Laboratório de Neurofarmacologia Molecular, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil.
authors.forename: Cristoforo
authors.identifier: 0000-0002-1206-0882
authors.initials: C
authors.lastname: Scavone
authors.affiliation: Laboratório de Biologia do Sistema Imune, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, Brazil.
authors.forename: Alexandre
authors.identifier: 0000-0001-9432-9701
authors.initials: A
authors.lastname: Morrot
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Imunologia Tumoral, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, Brazil.
authors.forename: Vivian Mary
authors.initials: VM
authors.lastname: Rumjanek
authors.affiliation: Centro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil ; Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodrigues-Mascarenhas
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010042:Ouabain / Q000627:therapeutic use*; D010538:Peritonitis / Q000139:chemically induced* / Q000188:drug therapy*; D011897:Random Allocation; D015054:Zymosan / Q000633:toxicity*
chemical_list: D010042:Ouabain; D015054:Zymosan